心力衰竭管理发展历程

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1、Management of Heart Failure:Past,Present and FutureLexin Wang,M.D.,Ph.D.,FCSANZProfessor of Clinical PharmacologyHead,Cardiovascular Research Objectives History and pathogenesis Epidemiology and risk factors Current management Future directionsKatz,A.M.Circ Heart Fail 2008;1:63-71Katz,A.M.Circ Heart

2、 Fail 2008;1:63-71William Harvey,1628William 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.Epigenetic

3、s(实验实验胚胎学胚胎学)Katz,A.M.Circ Heart Fail 2008;1:63-71Katz,A.M.Circ Heart Fail 2008;1:63-71Changing management of heart failure over the past 40 yearsChanging management of heart failure over the past 40 yearsCHF-Prevalence Approximately 5.5 million Americans have CHF(2.2%of the population)550,000 new c

4、ases annually Accounts for 12 million clinic visits per year Estimated health care costs in 2004 is US$28.8 billionCHF 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

5、 the countryAge-related prevalence of CHF American National HF project 34,587 hospitalized patientsAge(median,yrs)73Gender(female,%)59%History(%)hypertension61%coronary artery disease56%diabetes38%COPD33%atrial fibrillation30%Havranek EP et al.Am Heart J 2002;143:412-417Classification of CHF Systoli

6、c 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 CHFManagement of CHF Life style changes Pharmacological Surg

7、ical Devices CABG,PCI Cardiac transplantationDrug therapy STEP 1Confirm 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

8、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-indicatedDrug 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 I

9、nitiate spironolactone first followed by digoxin,both at a low dose and then up-titrate,check tolerability and blood chemistry.Co-operative North candinavian Enalapril Survival tudy I CONSENSUS I N Engl J Med 1987;316:14291435Studies of Left Ventricular Dysfunction SOLVD(Treatment Study)SOLVD Invest

10、igators N Engl J Med 1991;325:293302 N Engl J Med 2003;349:18931906VALIANT:ResultsN Engl J Med 2003;349:18931906VALIANT:Adverse eventsUnited States Carvedilol Program(USCP)Packer M et al.N Engl J Med 1996;334:13491355Cardiac Insufficiency Bisoprolol Study II CIBIS II)CIBIS II Investigators,Lancet 19

11、99;359:913 Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure(MERIT-HF)Hjalmarson A et al.Lancet 1999;353:20012007Remme,W.J.et al.J Am Coll Cardiol 2007;49:963-971Combined End Point of any MI,Unstable Angina,and StrokeRemme,W.J.et al.J Am Coll Cardiol 2007;49:963-971Death Aft

12、er a Nonfatal Myocardial Infarction or Nonfatal StrokeCCBs: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 b

13、lockers such as verapamil and diltiazem are contraindicated in patients with systolic heart failureElectromechanical 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 hea

14、rt65-year-old male,LBBB,LVEF 20%0.550.01(0.35 to 0.87)QRS 160 ms0.630.05(0.40 to 0.997)Female gender0.470.01(0.27 to 0.82)NYHA class IV2.620.01(1.61 to 4.26)Renal dysfunction1.690.03(1.06 to 2.69)TABLE 2.Risk of Sudden Cardiac Death Risk of Sudden Cardiac DeathSaxon LA et al.Circulation.2006;114:276

15、6-72.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 Ther

16、apies 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.adenovir

17、us)A method of delivery of these vectors Identification of appropriate gene targets,e.g.cardiac S100A1,a calcium binding gene,and sarcoplasmic reticular Ca2+gene Mechanical assistance Cardiac transplantation will always be limited the availability of donor hearts Ventricular assist devices(VADs)Main

18、ly used as bridges to transplantation As destination therapy?REMATCH trial:encouraging but the device was too large with many complications Ventricular assist devices(VADs)Current effort Reduce the incidence of complications and size of the device Indications for VADs are expected to expand quickly

19、in the next five years to provide destination therapy Conclusions The field of HF study is now at a historic juncture The pandemic of HF is increasing rapidly because of the aging population and increased number of survival patients following MI Studies on prevention and management of HF is accelera

20、ting Conclusions(continued)Advances in genetics,cell biology and molecular pharmacology will enhance understanding of the causes of HF Currently used ACEI,beta-blockers and CRT have clear benefits to clinical outcomes of HF Development in bioengineering could have an enormous beneficial impact on bo

21、th incidence and managementChronic heart failure(CHF)Definition a complex clinical syndrome with typical clinical symptoms that can occur at rest or on effort,and is characterised by objective evidence of an underlying structural abnormality or cardiac dysfunction that impairs the ventricle to fill

22、with or eject blood The term congestive heart failure is no longer used.MADIT-IIMoss AJ.N Engl J Med.2002;346:877-83.DefibrillatorConventionalP=0.0071.00.90.80.70.60.0Probability of Survival01234YearNo.At RiskDefibrillator 742502(0.91)274(0.94)110(0.78)9Conventional 490329(0.90)170(0.78)65(0.69)3 No

23、n-pharmacological Physical activity tailored to individuals Walk Slow walking at home 10-30 min a day,7 days a week Class IV patients require gentle mobilisation as symptoms allow Bed rest for those with acute deterioration of symptoms Non-pharmacological Sodium restriction 3 g sodium/day No more th

24、an 2 L fluid intake per day Daily weighing Weight variation should be 2 kg in two consecutive daysKatz,A.M.Circ Heart Fail 2008;1:63-71Katz,A.M.Circ Heart Fail 2008;1:63-71Two views of the circulationTwo views of the circulationStarling curveKatz,A.M.Circ Heart Fail 2008;1:63-71Katz,A.M.Circ Heart Fail 2008;1:63-71Proliferative signaling pathways that mediate cardiac hypertrophyProliferative signaling pathways that mediate cardiac hypertrophy