心力衰竭管理發(fā)展歷程

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

2、71Katz, A. M. Circ Heart Fail 2008;1:63-71William Harvey, 1628William Harvey, 1628整理課件 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. Maladaptiv

3、e hypertrophy 8. Genomics 9. Epigenetics (實驗胚胎學(xué)實驗胚胎學(xué))整理課件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 years整理課件CHF-Prevalence Approximately 5.5 million

4、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整理課件CHF prevalence- Australia 2% of adult population Approximately 241,000 patients 30,000 new cases each year 42,000 hospitali

5、sations in 2004-2005 Accounts for 0.8% of all hospitalisations in the country整理課件Age-related prevalence of CHF 整理課件整理課件American National HF project 34,587 hospitalized patientsAge (median, yrs)73Gender (female, %)59%History (%)hypertension61%coronary artery disease56%diabetes38%COPD33%atrial fibrill

6、ation30% Havranek EP et al. Am Heart J 2002;143:412-417整理課件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 d

7、ysfunction Accounts 40% of all CHF整理課件Management of CHF Life style changes Pharmacological Surgical Devices CABG, PCI Cardiac transplantation整理課件Drug therapy STEP 1Confirm left ventricular systolic dysfunction (LVSD) by Echocardiography Radionuclide ventriculography, or Radiological left ventricular

8、 angiography 整理課件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整理課件Drug therapy STEP 3 Initiate second-line therapy in

9、 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.整理課件Co-operative North candinavian Enalapril Survival tu

10、dy I CONSENSUS I N Engl J Med 1987; 316:142914358 80 07 70 01 10 02 20 03 30 04 40 05 50 06 60 00 01 12 23 34 45 56 67 78 89 91 10 01 11 11 12 2F Fo ol l l l o ow w - - u up p ( (m m o on nt th hs s) )M M o or rt ta al l i i t t y y( (% % ) )E En na al l a ap pr ri i l lP Pl l a ac ce eb bo oR R i i

11、 s sk k r re ed du uc ct ti i o on n 4 40 0% %p p= =0 0. . 0 00 02 2整理課件Studies of Left Ventricular Dysfunction SOLVD (Treatment Study) SOLVD Investigators N Engl J Med 1991; 325:293302 0 01 10 02 20 03 30 04 40 05 50 00 06 61 12 21 18 82 24 43 30 03 36 64 42 24 48 8P Pl l a ac ce eb bo oE En na al

12、l a ap pr ri i l lF Fo ol l l l o ow w - - u up p ( (m m o on nt th hs s) )M M o or rt ta al l i i t t y y( (% % ) )0 01 10 02 20 03 30 04 40 05 50 00 06 61 12 21 18 82 24 43 30 03 36 64 42 24 48 8P Pl l a ac ce eb bo oE En na al l a ap pr ri i l lF Fo ol l l l o ow w - - u up p ( (m m o on nt th hs

13、 s) )M M o or rt ta al l i i t t y y( (% % ) )R R i i s sk k r re ed du uc ct ti i o on n 1 16 6% %p p= =0 0. . 0 00 03 36 6整理課件N Engl J Med 2003; 349: 18931906VALIANT: Results整理課件N Engl J Med 2003; 349: 18931906VALIANT: Adverse events整理課件United States Carvedilol Program (USCP)Packer M et al. N Engl

14、 J Med 1996; 334:134913555 55 56 60 06 65 57 70 07 75 58 80 08 85 59 90 09 95 51 10 00 0C C a ar rv ve ed di i l l o ol lP Pl l a ac ce eb bo oD D u ur ra at ti i o on n o of ft th he er ra ap py y ( (d da ay ys s) )R R i i s sk k r re ed du uc ct ti i o on n 6 65 5% %p p= =0 0. . 0 00 00 01 1S Su u

15、r rv vi i v va al l( (% % ) )0 05 50 01 10 00 01 15 50 02 20 00 02 25 50 03 35 50 04 40 00 03 30 00 0整理課件Cardiac Insufficiency Bisoprolol Study II CIBIS II) CIBIS II Investigators, Lancet 1999; 359:913 0 06 60 08 80 01 10 00 00 02 20 00 04 40 00 06 60 00 08 80 00 0T Ti i m m e e a af ft te er ri i n

16、 nc cl l u us si i o on n ( ( d da ay ys s) )S Su ur rv vi i v va al l( (% % ) )B B i i s so op pr ro ol l o ol lP Pl l a ac ce eb bo oR R i i s sk k r re ed du uc ct ti i o on n 3 34 4% %p p 0 0. . 0 00 00 01 1整理課件 Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF

17、) Hjalmarson A et al. Lancet 1999; 353:200120070 05 51 01 01 51 52 02 00 03 36 69 91 21 21 51 51 81 82 12 1Follow- u p ( MFollow- u p ( Mo on nt th hs)s)Morta li t yMorta li t y(%)(%)P l aceboP l aceboM e topro l o lM e topro l o lR isk re d u c t i o n 34%R isk re d u c t i o n 34%p = 0.006 2p = 0.

18、006 2整理課件Remme, W. J. et al. J Am Coll Cardiol 2007;49:963-971Combined End Point of any MI, Unstable Angina, and Stroke整理課件Remme, W. J. et al. J Am Coll Cardiol 2007;49:963-971Death After a Nonfatal Myocardial Infarction or Nonfatal Stroke整理課件CCBs: NHF recommendations Amlodipine and felodipine can b

19、e 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整理課件Electr

20、omechanical 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 heart65-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 gender0.4

21、70.01(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.整理課件 Indications for CRT NYHA III-IV, despite optimal medical therapy Dilated heart failure wit

22、h EF120 ms Sinus rhythm整理課件 Future directions Cell-Based Therapies Embryonic stem cells Bone marrow cells (contains stem cells and progenitor cells) Circulating blood-derived progenitor cells (EPCs)整理課件 Cell-Based Therapies Several small trials demonstrated improvement of LV function Challenges Curr

23、ent studies aretoo small to assess clinical outcomes Method of preparation and delivery uncertain The best type of cells to use is still unclear整理課件 Gene Therapy Major challenges Development of an ideal vector (e.g. adenovirus) A method of delivery of these vectors Identification of appropriate gene

24、 targets, e.g. cardiac S100A1, a calcium binding gene, and sarcoplasmic reticular Ca2+ gene整理課件 Mechanical assistance Cardiac transplantation will always be limited the availability of donor hearts Ventricular assist devices (VADs) Mainly used as bridges to transplantation As destination therapy? RE

25、MATCH trial: encouraging but the device was too large with many complications整理課件 Ventricular assist devices (VADs) Current effort Reduce the incidence of complications and size of the device Indications for VADs are expected to expand quickly in the next five years to provide destination therapy整理課

26、件 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 accelerating 整理課件 Conclusions (continued) Advances in geneti

27、cs, 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 both incidence and management整理課件整理課件Chronic

28、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 with or eject blood The term congestive heart failure is no longer used.整理課件MADIT-IIMoss AJ. N Engl J Med. 2002;346:877-83.Defibrill