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Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Management of Heart Failure:,Past,Present and Future,Lexin Wang,M.D.,Ph.D.,FCSANZ,Professor of Clinical Pharmacology,Head,Cardiovascular Research,Objectives,History and pathogenesis,Epidemiology and risk factors,Current management,Future directions,Katz,A.M.Circ Heart Fail 2008;1:63-71,William Harvey,1628,Changing views of heart failure,1.A clinical syndrome,2.A circulatory disorder,3.Altered architecture of the heart,4.Abnormal hemodynamics,5.Disordered fluid balance,6.Biochemical abnormalities,7.Maladaptive hypertrophy,8.Genomics,9.Epigenetics(,实验胚胎学,),Katz,A.M.Circ Heart Fail 2008;1:63-71,Changing management of heart failure over the past 40 years,CHF-Prevalence,Approximately 5.5 million Americans have CHF(2.2%of the population),550,000 new cases annually,Accounts for 12 million clinic visits per year,Estimated health care costs in 2004 is US$28.8 billion,CHF prevalence-Australia,2%of adult population,Approximately 241,000 patients,30,000 new cases each year,42,000 hospitalisations in 2004-2005,Accounts for 0.8%of all hospitalisations in the country,Age-related prevalence of CHF,American National HF project 34,587 hospitalized patients,Age(median,yrs)73,Gender(female,%)59%,History(%),hypertension61%,coronary artery disease56%,diabetes38%,COPD33%,atrial fibrillation30%,Havranek EP et al.,Am Heart J,2002;143:412-417,Classification of CHF,Systolic CHF,Weakened ability of the ventricles to contract,Heart failure with preserved systolic function,Impaired diastolic filling of the left ventricle,resulting in high filling pressure,with or without systolic dysfunction,Accounts 40%of all CHF,Management of CHF,Life style changes,Pharmacological,Surgical,Devices,CABG,PCI,Cardiac transplantation,Drug therapy,STEP 1,Confirm left ventricular systolic dysfunction(LVSD)by,Echocardiography,Radionuclide ventriculography,or,Radiological left ventricular angiography,Drug therapy,STEP 2,Initiate first-line therapy in all patients with heart failure due to LVSD with,a diuretic and an ACE inhibitor for NYHA class I-IV,and,a beta-blocker for NYHA class II-III,unless these are contra-indicated,Drug therapy,STEP 3,Initiate second-line therapy in patients with persistent signs and symptoms of heart failure(NYHA class III/IV)with spironolactone and digoxin,Initiate spironolactone first followed by digoxin,both at a low dose and then up-titrate,check tolerability and blood chemistry.,Co,-operative,N,orth,S,candinavian,En,alapril,Su,rvival,S,tudy,I,CONSENSUS I,N Engl J Med 1987;,316:,14291435,S,tudies,o,f,L,eft,V,entricular,D,ysfunction SOLVD(Treatment Study),SOLVD Investigators N Engl J Med 1991;,325,:293302,N Engl J Med 2003;349:18931906,VALIANT:Results,N Engl J Med 2003;349:18931906,VALIANT:Adverse events,U,nited,S,tates,C,arvedilol,P,rogram(USCP),Packer M et al.N Engl J Med 1996;,334,:13491355,C,ardiac,I,nsufficiency,Bi,soprolol,S,tudy II,(,CIBIS II),CIBIS II Investigators,Lancet 1999;,359:,913,Me,toprolol CR/XL,R,andomized,I,ntervention,T,rial in Congestive,H,eart,F,ailure(MERIT-HF),Hjalmarson A et al.Lancet 1999;,353,:20012007,Remme,W.J.et al.J Am Coll Cardiol 2007;49:963-971,Combined End Point of any MI,Unstable Angina,and Stroke,Remme,W.J.et al.J Am Coll Cardiol 2007;49:963-971,Death After a Nonfatal Myocardial Infarction or Nonfatal Stroke,CCBs:NHF recommendations,Amlodipine and felodipine,can be used to treat comorbidities such as hypertension and CHD in patients with systolic CHF,They have been shown to neither increase nor decrease mortality.,Non-dihydropyridine calcium-channel blockers such as,verapamil and diltiazem,are contraindicated in patients with systolic heart failure,Electromechanical dysfunction,Defined as,any abnormality,in the generation or transmission of electrical impulses that results in clinically significant alteration in the mechanical function of the heart,65-year-old male,LBBB,LVEF 20%,0.55,0.01,(0.35 to 0.87),QRS 160 ms,0.63,0.05,(0.40 to 0.997),Female gender,0.47,0.01,(0.27 to 0.82),NYHA class IV,2.62,0.01,(1.61 to 4.26),Renal dysfunction,1.69,0.03,(1.06 to 2.69),TABLE 2.Risk of Sudden Cardiac Death,Risk of Sudden Cardiac Death,Saxon LA et al.Circulation.,2006;114:2766-72.,Indications for CRT,NYHA III-IV,despite optimal medical therapy,Dilated heart failure with EF120 ms,Sinus rhythm,Future directions,Cell-Based Therapies,Embryonic stem cells,Bone marrow cells(contains stem cells and progenitor cells),Circulating blood-derived progenitor cells(EPCs),Cell-Based Therapies,Several small trials demonstrated improvement of LV function,Challenges,Current studies aretoo small to assess clinical outcomes,Method of preparation and delivery uncertain,The best type of cells to use is still unclear,Gene Therapy,Major challenges,Development of an ideal vector(e.g.adenovirus),A method of delivery of these vectors,Identification of appropriate gene targets,e.g.cardiac S100A1,a calcium binding gene,
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