心力衰竭管理發(fā)展歷程課件

1、Management of Heart Failure: Past, Present and FutureLexin Wang, M.D., Ph.D., FCSANZProfessor of Clinical PharmacologyHead, Cardiovascular Research Management of Heart Failure: PObjectivesHistory and pathogenesisEpidemiology and risk factorsCurrent managementFuture directionsObjectivesHistory and pa

2、thogeKatz, A. M. Circ Heart Fail 2008;1:63-71William Harvey, 1628Katz, A. M. Circ Heart Fail 20Changing 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. Ma

3、ladaptive hypertrophy 8. Genomics 9. Epigenetics (實驗胚胎學(xué))Changing views of heart failuKatz, A. M. Circ Heart Fail 2008;1:63-71Changing management of heart failure over the past 40 yearsKatz, A. M. Circ Heart Fail 20CHF-PrevalenceApproximately 5.5 million Americans have CHF (2.2% of the population)550

4、,000 new cases annuallyAccounts for 12 million clinic visits per yearEstimated health care costs in 2004 is US $28.8 billionCHF-PrevalenceApproximately 5.CHF prevalence- Australia2% of adult populationApproximately 241,000 patients30,000 new cases each year42,000 hospitalisations in 2004-2005Account

5、s for 0.8% of all hospitalisations in the countryCHF prevalence- Australia2% ofAge-related prevalence of CHF Age-related prevalence of CHF 心力衰竭管理發(fā)展歷程課件American National HF project 34,587 hospitalized patientsAge (median, yrs)73Gender (female, %)59%History (%)hypertension61%coronary artery disease56%

6、diabetes38%COPD33%atrial fibrillation30% Havranek EP et al. Am Heart J 2002;143:412-417American National HF project 3Classification of CHFSystolic CHFWeakened ability of the ventricles to contractHeart failure with preserved systolic functionImpaired diastolic filling of the left ventricle, resultin

7、g in high filling pressure, with or without systolic dysfunctionAccounts 40% of all CHFClassification of CHFSystolic Management of CHFLife style changesPharmacologicalSurgicalDevicesCABG, PCICardiac transplantationManagement of CHFLife style cDrug therapySTEP 1Confirm left ventricular systolic dysfu

8、nction (LVSD) by EchocardiographyRadionuclide ventriculography, or Radiological left ventricular angiography Drug therapySTEP 1Drug therapySTEP 2Initiate first-line therapy in all patients with heart failure due to LVSD witha diuretic and an ACE inhibitor for NYHA class I-IV, and a beta-blocker for

9、NYHA class II-III, unless these are contra-indicatedDrug therapySTEP 2Drug therapySTEP 3Initiate second-line therapy in patients with persistent signs and symptoms of heart failure (NYHA class III/IV) with spironolactone and digoxinInitiate spironolactone first followed by digoxin, both at a low dos

10、e and then up-titrate, check tolerability and blood chemistry.Drug therapySTEP 3Co-operative North Scandinavian Enalapril Survival Study I CONSENSUS I N Engl J Med 1987; 316:14291435Co-operative North ScandinaviaStudies of Left Ventricular Dysfunction SOLVD (Treatment Study) SOLVD Investigators N En

11、gl J Med 1991; 325:293302 Studies of Left Ventricular DyN Engl J Med 2003; 349: 18931906VALIANT: ResultsN Engl J Med 2003; 349: 18931N Engl J Med 2003; 349: 18931906VALIANT: Adverse eventsN Engl J Med 2003; 349: 18931United States Carvedilol Program (USCP) Packer M et al. N Engl J Med 1996; 334:1349

12、1355United States Carvedilol ProgrCardiac Insufficiency Bisoprolol Study II (CIBIS II) CIBIS II Investigators, Lancet 1999; 359:913 Cardiac Insufficiency Bisoprol Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF) Hjalmarson A et al. Lancet 1999; 353:20012007 Metop

13、rolol CR/XL Randomized Remme, 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 Remme, W. J. et al. J Am Coll Cardiol 2007;49:963-971Death After a Nonfatal Myocardial Infarction or Nonfatal StrokeRemme, W. J. et al. J

14、 Am Coll CCBs: NHF recommendationsAmlodipine and felodipine can be used to treat comorbidities such as hypertension and CHD in patients with systolic CHFThey have been shown to neither increase nor decrease mortality.Non-dihydropyridine calcium-channel blockers such as verapamil and diltiazem are co

15、ntraindicated in patients with systolic heart failureCCBs: NHF recommendationsAmlodElectromechanical dysfunctionDefined as any abnormality in the generation or transmission of electrical impulses that results in clinically significant alteration in the mechanical function of the heart65-year-old mal

16、e, 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;114:2766-72.Variabl

17、e Sudden Cardiac Death Indications for CRT NYHA III-IV, despite optimal medical therapyDilated heart failure with EF120 msSinus rhythmIndications for CRT Future directionsCell-Based TherapiesEmbryonic stem cellsBone marrow cells (contains stem cells and progenitor cells)Circulating blood-derived pro

18、genitor cells (EPCs)Future directionsCell-Based TherapiesSeveral small trials demonstrated improvement of LV functionChallengesCurrent studies aretoo small to assess clinical outcomesMethod of preparation and delivery uncertainThe best type of cells to use is still unclearCell-Based TherapiesGene Th

19、erapyMajor challengesDevelopment of an ideal vector (e.g. adenovirus)A method of delivery of these vectorsIdentification of appropriate gene targets, e.g. cardiac S100A1, a calcium binding gene, and sarcoplasmic reticular Ca2+ geneGene TherapyMechanical assistanceCardiac transplantation will always

20、be limited the availability of donor heartsVentricular assist devices (VADs)Mainly used as bridges to transplantationAs destination therapy?REMATCH trial: encouraging but the device was too large with many complicationsMechanical assistanceVentricular assist devices (VADs)Current effortReduce the in

21、cidence of complications and size of the deviceIndications for VADs are expected to expand quickly in the next five years to provide destination therapyVentricular assist devices (VAConclusionsThe field of HF study is now at a historic junctureThe pandemic of HF is increasing rapidly because of the

22、aging population and increased number of survival patients following MIStudies on prevention and management of HF is accelerating ConclusionsConclusions (continued)Advances in genetics, cell biology and molecular pharmacology will enhance understanding of the causes of HFCurrently used ACEI, beta-bl

23、ockers and CRT have clear benefits to clinical outcomes of HFDevelopment in bioengineering could have an enormous beneficial impact on both incidence and managementConclusions (continued)心力衰竭管理發(fā)展歷程課件Chronic heart failure (CHF)Definitiona complex clinical syndrome with typical clinical symptoms that

24、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 with or eject bloodThe term congestive heart failure is no longer used.Chronic heart failure (CHF)DefMADIT-IIMoss AJ. N Engl J Med. 2002;346:877-83.DefibrillatorConventionalP = 0.0071.00.90.80.70.60.0Probability of Survival01234YearNo. At RiskDefibrillator742502 (0