脑钠肽（bnp）与心力衰竭的研究进展教学课件幻灯

脑钠肽(BNP)与心力衰竭的 研究进展 北京世纪坛医院 北京大学第九临床医学院 杨水祥 教授 2009年8月20日 Outcomes in Patients Hospitalized With HF Jong P et al. Arch Intern Med. 2002;162:1689 0 25 50 75 100 20% 50% 30 days 6 mo Hospital Readmissions 0 25 50 75 100 12% 50% 30 days 12 mo Mortality 33% 5 yr Median hospital LOS: 6 days Annual mortality rate- NYHA class III HF- 12% COPERNICUS DATA NYHA class II HF- 7% SCD-HeFT DATA 在美国，因心衰入院人数=每年一百万。总 费用=560亿美元 住院治疗花费中，70-75%直接用于患者护 理 心衰住院治疗后再入院=6个月内达45% 心衰的治疗负担 Increased morbidity and mortality Diuretic therapy Impaired renal function Decreased renal perfusion Diuretic resistance Diminished blood flow Neurohormonal activation Potential Deleterious Effects of Diuretics and Cardiorenal Syndrome of HF Neurohormonal activation Vasoconstriction Congestion Pathologic remodeling Hemodynamic (balanced vasodilation) lveins larteries lcoronary arteries B-Type Natriuretic Peptide (BNP) Neurohumoral aldosterone endothelin norepinephrine Renal diuresis natriuresis GFR D RI M K R G SS S S G L G F C C SS G S GQV M KVL R R H KP S Cardiac llusitropic lantifibrotic lanti-remodeling Jamieson and Palade. J Cell Biol. 1964;23:151. Natriuretic Peptides: The Heart as a Secretory Organ Atrial stretch receptors link blood volume to renal function Distension of a balloon catheter in atria of dogs resulted in diuresis Henry et al (1956) Secretory granules discovered in the atria Kisch (1956) Jamieson and Palade (1964) BNP was characterized by amino acid sequence and DNA clones Sudoh et al (1988) Seilhamer et al (1989) Natriuretic Peptides Adapted from Burnett JC. J Hypertens. 2000;17(Suppl 1):S37-S43. ANP = Atrial Natriuretic Peptide BNP = B-type Natriuretic Peptide CNP = C-type Natriuretic Peptide PeptidePrimary OriginStimulus of Release ANPCardiac atriaAtrial distension BNPVentricular myocardium Ventricular overload CNPEndothelium Endothelial stress Natriuretic Peptides: Origin and Stimulus of Release H2N H2N COOH COOH COOH pro-BNP (aa1 - aa108) Cleavage BNP (aa77 - aa108) NT-proBNP (aa1 - aa76) H P L G S P G S A S Y T L R A P RS P K M V Q G S G C F C R K M D RI S S S S G L C C K V L R R H HPLGSPGSASYTLR APR S P K M V Q G S G C F C R K M D RI S S S S G L C C K V L R R H H2N 1 10 70 76 80 90 100 108 1107076 MyocardMyocard BloodBlood pre-proBNP 1 - 134 (134 Aa) Signal peptide (26 Aa) 28 17 14 6 3 kDa Rec. A B C D E blank Rec. Clinical BNP Results pg/mL: A BCDE Maisel3920 3720 4010 2090 127 in-house Triage 1140 1440 1260 1570 584 在心衰患者中在心衰患者中BNPBNP主要的形式是主要的形式是 proBNPproBNP proBNP BNP 5 CHF patients: Liang, Maisel et al., JACC 2007 All55-64 65-74 75+ Age All non-CHF Non-CHF Male Non-CHF Female BNP Levels in Non-CHF Patients BNP (pg/mL) 0 50 100 (n=478) ADHFADHF中的中的BNPBNP水平和院内死亡率水平和院内死亡率 BNPBNP水平的分布水平的分布 (pg/mL) 在初期评估中，77,467例患者中有 48,629 例 (63%)作了BNP评估. 在ADHERE项目中仅 3.3%的患者 初始 BNP水平 238 P13 0 pg/mL only multivariate predictor of SD (P=0.0006) Berger. Circulation. 2002;105:2392-2397. 连续BNP测定能指导住院治疗吗? Courtesy of Damien Logeart. 住院期间BNP值 Logeart D, et al, JACC, 18 February 2004, Volume 43, Issue 4 Pages 635-641 BNPBNP在急性充血性心力衰竭在急性充血性心力衰竭 住院治疗和结果评价住院治疗和结果评价 0 500 1000 1500 2000 2500 admission follow-up (pg/mL) n=22Endpoints:13 deaths 9 re-admissions (30d) n=50No Endpoints BNP +233 pg/BNP +233 pg/ mL BNP -215 pg/BNP -215 pg/mL Cheng,Maisel. JACC 2001;37:386-91 入院和出院前入院和出院前BNPBNP值值(pg/(pg/mLmL) ) 和住院时间和住院时间( (天天) ) 12 10 8 6 4 2 0 BNP on admission BNP on discharge Length of stay 398 123 481 127 1037 729 2.2 6.86.9 0 200 400 600 800 1000 1200 BNP1BNP2LOS pg/ml BNP 250 pg/ml 根据出院前根据出院前 BNPBNP水平作出的水平作出的Kaplan-Kaplan- MeierMeier曲线显示累积死亡率和再入院率曲线显示累积死亡率和再入院率 BNP 250 pg/ml BNP 80 pg/mL (n=1274) Percent of Patients (%) Death 30 days P 400 pg/mL CHF very unlikely (2%) Baseline LV dysfunction, underlying cor pulmonale or acute pulmonary embolism? YesNo Possible exacerbation of CHF (25%) CHF likely (75%) CHF very likely (95%) Heart Failure Diagnostic Algorithm BNP levels and NYHA class of HF NYHA ClassBNP level (pg/ml) I244 + 286 II389 + 374 III640 + 447 IV817 + 435 Nesiritide Identical to human BNP Causing vasodilation and decrease LV filling pressure Decrease pulmonary capillary wedge pressure Improves patients symptoms nesiritide resulted in improvement in hemodynamics and some self-reported symptoms more effectively and with fewer adverse effects than intravenous nitroglycerin (VMAC trial ) Hemodynamic Effects of Nesiritide vs Placebo vs IV NTG * * * * Publication Committee for the VMAC Investigators. JAMA. 2002;287:1531 During 3-hr placebo period Placebon = 62 IV NTGn = 60 Nesiritiden = 124 After 3-hr period IV NTGn = 92 Nesiritiden = 154 *P0.05 vs placebo P0.05 vs IV NTG PCWP Placebo PCWP IV NTG PCWP Nesiritide End of Placebo-Controlled Period Time on Study Drug (hr) 00.250.5 12369 12 24 36 48 9 8 7 6 5 4 3 2 1 0 * * Change From Baseline in PCWP (mm Hg) 2424小时治疗期间小时治疗期间 BNP BNP 和和PAW*PAW*水平的变化水平的变化 Msaisel, A. et al. J Cardiac Failure, Vol. 7, No. 1, 2001 N = 15 (responders) PAW (mm Hg) Hours BNP (pg/ml) 15 17 19 21 23 25 27 29 31 33 baseline4812162024 600 700 800 900 1000 1100 1200 1300 PAW BNP *Pulmonary artery wedge. VMAC: Dyspnea Improvement *Added to standard care Publication Committee for the VMAC Investigators. JAMA. 2002;287:1531 Dyspnea at 3 hr Proportion of Subjects (%) Nitroglycerin* (n = 143) Nesiritide* (n = 204) Placebo* (n = 142) 40 30 20 10 0 10 20 30 40 50 60 70 80 90 100 P=0.191 P=0.034 Markedly better Moderately better Minimally better No change Minimally markedly worse THE NAPA TRIAL: Nesiritide Administered Peri-Anesthesia in Patients Undergoing Cardiac Surgery Mark J. Russo, MD, MS Division of Cardiothoracic Surgery & International Center for Health Outcomes and Innovation Research College of Physicians and Surgeons, Columbia University, New York, NY NAPA TRIAL DESIGN Multi-center (54 centers) Randomized Double-blind Placebo-controlled Introduction Methods Results Summary NAPA TRIAL DESIGN LV dysfunction (EF40%) NYHA Class II - IV undergoing CABG MVS using cardiopulmonary bypass Introduction Methods Results Summary EXCLUSION CRITERIA Planned AVR/r Off-pump Ongoing or chronic dialysis Hemodynamic criteri