心力衰竭临床治疗进展阻滞剂的应用首都医科大学附属北京友谊医院沈潞华1流行病学美国FRAMINGHAM心脏研究2000发病率年均心衰死亡率:3050%流行病学美国FRAMINGHAM心脏研究20005年存活率中国心衰的发病率3574岁居民，15518人（10个省市20个城乡 抽样调查） 心率发病率0.9% 男性0.7% 女性1.0%北方1.4% 南方0.5%城市1.1% 农村0.8% 随着年龄的增高，患病率显著上升心力衰竭的形成过程心力衰竭的形成过程各种原因所致的心脏损害心脏结构的改变心脏结构的改变心肌重量心肌重量心室容量心室容量心室形态心室形态心室重构心室重构心脏功能减退心脏功能减退, ,心力衰竭心力衰竭AMI AMI 后神经内分泌激活界导左室重构的结果后神经内分泌激活界导左室重构的结果AMI血液动力学异常 (SV EF CO LVEDP 心室扩张, 室壁张力增加）神经内分泌激活(RAAS SNS细胞因子)心肌细胞肥厚心肌间质纤维化 心肌细胞坏死 心肌毛细血管生长不足心功能受损,心肌缺血,心律失常左室重构进展,心力衰竭心衰时神经内分泌激活的危害性心衰时神经内分泌激活的危害性循环和组织中NE, ANG II, 醛固酮, 内皮素, 加压素等钠水潴留钠水潴留, , 血管收缩血管收缩室壁张力升高室壁张力升高, , 心脏毒性作用心脏毒性作用, , 刺激心肌纤维化刺激心肌纤维化促进心室重构促进心室重构, , 加速心衰进展加速心衰进展肾上腺素超负荷血液动力学超负荷心室重构心肌细胞肥大收缩功能异常细胞凋亡交感神经系统兴奋心力衰竭Cir 93;87(SVI):VI-40-48Plasma Plasma noradrenalinenoradrenaline and mortality and mortalityin congestive heart failure in congestive heart failureCHF过程心肌梗死后心室重构过程心肌梗死几小时后心肌梗死几小时几天心肌梗死几天几个月心衰恶化可能机制心衰病情加重心衰血肾素水平升高 血管紧张素升高交感神经系统 长期激活心脏处于极度 氧化应激状态对心脏产生毒性作用于心肌需氧增加心心脏脏交交感感神神经经活活性性 血血管管紧紧张张素素 IIII心心肌肌肥肥厚，厚， 凋凋亡，亡， 缺缺血，血， 心心律律失失常，常，心心肌肌重重构，构，纤纤维维化化心室重塑心室重塑 1 1受体受体 2 2受体受体 1 1受体受体 血管收缩血管收缩衰竭心肌-受体密度，非胞内重新分布受体总数表面受体反应性（脱敏）l主要下调为1， 2密度正常或相对提高l主要部位为内膜下选择性衰竭时其受体密度为外膜的63 5%（正常时应为115 6%）非均一下调的机制：血CA、局部NE释放心内膜外膜血流量代谢不同衰竭心肌受体的改变SNA增强是心衰的主要原因衰竭时的心肌1受体激酶mRNA水平减少*P 65 65 yearsyears n=1982n=1982 30%30% 37%37% 38%38% 43%43% 8%8% 61%61% 22%22% 38%38%All Cause All Cause MortalityMortalitySudden Sudden DeathDeathDeath/Death/ Worsening Worsening HFHFHosp for Hosp for worsening worsening HFHFRisk Risk r reductioneduction (%) (%)-60-60-50-50-40-40-30-30-20-20-10-100 010102020-70-70Why Do Physicians Not Give Beta-blockers to Patients?l lPatient is too old for Patient is too old for betabeta-blockers-blockersl lPatient has COPDPatient has COPDl lPatient has Diabetes mellitusPatient has Diabetes mellitusl lPatient has BP which is too lowPatient has BP which is too lowl lPatient has EF which is too lowPatient has EF which is too lowl lBetaBeta-blockers cause impotence, -blockers cause impotence, claudicationclaudication and and depressiondepressionl lCan only tolerate low doseCan only tolerate low dosel lToo expensive drugs -no cost-benefitToo expensive drugs -no cost-benefitMyths about side effects and tolerability:Meto CR/XL PlaceboNet difference Adverse event1 (Meto CR/XL-Placebo)n=1990n=2001 One year of treatmentInfection25874-0.8% Dyspnoea30270.1% Pulmonary oedema89-0.1% Bronchospasm68-0.1% COPD367-0.1% Haemoptysis17-0.3%Any respiratory AE 108 121-0.7%The MERIT-HF Study GroupRespiratory System Disorders: All AE/SAE ReportedRespiratory System Disorders: All AE/SAE Reported1One patient may have more than one AE in a system organ class2Pneumonia, Bronchitis or Respiratory infection3Chronic obstructive pulmonary diseaseWhy Do Physicians Not Give Beta-blockers to Patients?l lPatient is too old for Patient is too old for betabeta-blockers-blockersl lPatient has COPDPatient has COPDl lPatient has Diabetes mellitusPatient has Diabetes mellitusl lPatient has BP which is too lowPatient has BP which is too lowl lPatient has EF which is too lowPatient has EF which is too lowl lBetaBeta-blockers cause impotence, -blockers cause impotence, claudicationclaudication and and depressiondepressionl lCan only tolerate low doseCan only tolerate low dosel lToo expensive drugs -no cost-benefitToo expensive drugs -no cost-benefitMyths about side effects and tolerability:MERIT-HF: Risk Reductions in Diabetics PatientsDeedwania P et al. ACC 2002-30-30-20-20-10-100 01010 All All DeathsDeathsAll deaths/All deaths/ All HospAll HospAll Deaths/ All Deaths/ HF HospHF Hosp 21% 21% 15% 15% 29% 29%Risk reduction* Risk reduction* vsvs placebo (%) placebo (%)n=984n=984* * Time to first eventTime to first event5 5-5-5-15-15-25-25Meto CR/XL PlaceboNet difference Adverse event (Meto CR/XL-Placebo)n=1990n=2001 One year of treatmentHyperglycaemic reaction24200.2%Hypoglycaemic reaction430.1%Diabetic ulcer44 - New onset diabetes mellitus34-0.1%Total number of patients35310.2%The MERIT-HF Study Group, JAMA 2000;283:1295-1302Diabetes Mellitus: All AE/SAE ReportedDiabetes Mellitus: All AE/SAE ReportedThe MERIT-HF Study GroupWhy Do Physicians Not Give Beta-blockers to Patients?l lPatient is too old for Patient is too old for betabeta-blockers-blockersl lPatient has COPDPatient has COPDl lPatient has Diabetes mellitusPatient has Diabetes mellitusl lPatient has BP which is too lowPatient has BP which is too lowl lPatient has EF which is too lowPatient has EF which is too lowl lBetaBeta-blockers cause impotence, -blockers cause impotence, claudicationclaudication and and depressiondepressionl lCan only tolerate low doseCan only tolerate low dosel lToo expensive drugs -no cost-benefitToo expensive drugs -no cost-benefitMyths about side effects and tolerability:SBP: SBP: 120 (mean 142 mm Hg)SBP: 120 (mean 142 mm Hg)144/213144/213 167/226167/226Total mortality/hospitalization for