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[AHA2006]N-Terminal proB-type Natriuretic Peptide Improves the Management of Patients with Suspected Acute Heart FailurePrimary Results of the Canadian Multicenter IMPROVE-CHF Study加拿大多中心IMPROVE-CHF 研究初步结果表明N端BNP前体蛋白可改善对疑似急性心衰患者的处置
[2006/12/18 0:00:00]
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Gordon W. Moe, MD; Jonathan Howlett, MD; Hanna Zowall, PHD; for the Canadian Multicenter IMPROVE-CHF Study Investigators 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 that
 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 ED 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 ED visits and hospitalizations (US$5592 to US$4631 per patient, P=0.017). 
Summary and Conclusions 
Results of the IMPROVE-CHF trial show that in a universal access publicly-funded health care system that mandates judicious resource allocation, the use of NT-proBNP testing in conjunction with clinical assessment improves the overall management of patients presenting to ED with suspected acute HF, through the facilitation of diagnosis, risk stratification and cost savings that is accompanied by an improvement in selected outcomes. 
References 
1. American Heart Association. Heart Disease and Stroke Statistics - 2006 Update. Dallas, Texas: American Heart Association; 2006. 3 A.D. 9-15-2006. 2. Haldeman GA, Croft JB, Giles WH, Rashidee A. Hospitalization of patients with heart failure: National Hospital Discharge Survey, 1985 to 1995. Am Heart J 1999;137:352-360. 3. Lasser KE, Himmelstein DU, Woolhandler S. Access to care, health status, and health disparities in the United States and Canada: results of a cross-national population-based survey. Am J Public Health 2006;96:1300-1307. 4. Johansen H, Strauss B, Arnold JM, Moe G, Liu P. On the rise: The current and projected future burden of congestive heart failure hospitalization in Canada. Can J Cardiol 2003;19:430-435. 5. Jong P, Vowinckel E, Liu PP, Gong Y, Tu JV. Prognosis and determinants of survival in patients newly hospitalized for heart failure: a population-based study. Arch Intern Med 2002;162:1689-1694. 6. Lee DS, Austin PC, Rouleau JL, Liu PP, Naimark D, Tu JV. Predicting mortality among patients hospitalized for heart failure: derivation and validation of a clinical model. JAMA 2003;290:2581-2587. 7. Tsuyuki RT, Shibata MC, Nilsson C, Hervas-Malo M. Contemporary burden of illness of congestive heart failure in Canada. Can J Cardiol 2003;19:436-438. 8. Johansen H, Strauss B, Arnold JM, Moe G, Liu P. On the rise: The current and projected future burden of congestive heart failure hospitalization in Canada. Can J Cardiol 2003;19:430-435. 9. Tsuyuki RT, Shibata MC, Nilsson C, Hervas-Malo M. Contemporary burden of illness of congestive heart failure in Canada. Can J Cardiol 2003;19:436-438. 10. Harrison A, Morrison LK, Krishnaswamy P, Kazanegra R, Clopton P, Dao Q, Hlavin P, Maisel AS. B-type natriuretic peptide predicts future cardiac events in patients presenting to the emergency department with dyspnea. Ann Emerg Med 2002;39:131-138. 11. Januzzi JL, Jr., Camargo CA, Anwaruddin S, Baggish AL, Chen AA, Krauser DG, Tung R, Cameron R, Nagurney JT, Chae CU, Lloyd-Jones DM, Brown DF, Foran-Melanson S, Sluss PM, Lee-Lewandrowski E, Lewandrowski KB. The N-terminal Pro-BNP investigation of dyspnea in the emergency department (PRIDE) study. Am J Cardiol 2005;95:948-954. 12. Maisel AS, Krishnaswamy P, Nowak RM, McCord J, Hollander JE, Duc P, Omland T, Storrow AB, Abraham WT, Wu AH, Clopton P, Steg PG, Westheim A, Knudsen CW, Perez A, Kazanegra R, Herrmann HC, McCullough PA. Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med 2002;347:161-167. 13. McCullough PA, Nowak RM, McCord J, Hollander JE, Herrmann HC, Steg PG, Duc P, Westheim A, Omland T, Knudsen CW, Storrow AB, Abraham WT, Lamba S, Wu AH, Perez A, Clopton P, Krishnaswamy P, Kazanegra R, Maisel AS. B-type natriuretic peptide and clinical judgment in emergency diagnosis of heart failure: analysis from Breathing Not Properly (BNP) Multinational Study. Circulation 2002;106:416-422. 14. Moe GW. BNP in the Diagnosis and Risk Stratification of Heart Failure. Heart Fail Monit 2005;4:116-122. 15. Bayes-Genis A, Santalo-Bel M, Zapico-Muniz E, Lopez L, Cotes C, Bellido J, Leta R, Casan P, Ordonez-Llanos J. N-terminal probrain natriuretic peptide (NT-proBNP) in the emergency diagnosis and in-hospital monitoring of patients with dyspnoea and ventricular dysfunction. Eur J Heart Fail 2004;6:301-308. 16. Lainchbury JG, Campbell E, Frampton CM, Yandle TG, Nicholls MG, Richards AM. Brain natriuretic peptide and n-terminal brain natriuretic peptide in the diagnosis of heart failure in patients with acute shortness of breath. J Am Coll Cardiol 2003;42:728-735. 17. Bayes-Genis A, Santalo-Bel M, Zapico-Muniz E, Lopez L, Cotes C, Bellido J, Leta R, Casan P, Ordonez-Llanos J. N-terminal probrain natriuretic peptide (NT-proBNP) in the emergency diagnosis and in-hospital monitoring of patients with dyspnoea and ventricul




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