心力衰竭管理發(fā)展歷程

1、Management of Heart Failure: Past, Present and Future,Lexin Wang, M.D., Ph.D., FCSANZProfessor of Clinical PharmacologyHead, Cardiovascular Research,Objectives,History and pathogenesisEpidemiology and risk factorsCur

2、rent managementFuture 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

3、. Abnormal hemodynamics 5. Disordered fluid balance 6. Biochemical abnormalities 7. Maladaptive hypertrophy 8. Genomics 9. Epigenetics (實驗胚胎學(xué)),Katz, A. M. Circ Heart Fail 2008;1:63-71,Changing management of heart fa

4、ilure over the past 40 years,CHF-Prevalence,Approximately 5.5 million Americans have CHF (2.2% of the population)550,000 new cases annuallyAccounts for 12 million clinic visits per yearEstimated health care costs in 2

5、004 is US $28.8 billion,CHF prevalence- Australia,2% of adult populationApproximately 241,000 patients30,000 new cases each year42,000 hospitalisations in 2004-2005Accounts for 0.8% of all hospitalisations in the cou

6、ntry,Age-related prevalence of CHF,American National HF project 34,587 hospitalized patients,Age (median, yrs)73Gender (female, %)59%History (%)hypertension61%coronary artery disease56%diabetes38

7、%COPD33%atrial fibrillation30% Havranek EP et al. Am Heart J 2002;143:412-417,Classification of CHF,Systolic CHFWeakened ability of the ventricles to contractHeart failure with preserved systolic functi

8、onImpaired diastolic filling of the left ventricle, resulting in high filling pressure, with or without systolic dysfunctionAccounts 40% of all CHF,Management of CHF,Life style changesPharmacologicalSurgicalDevices

9、CABG, PCICardiac transplantation,Drug therapy,STEP 1Confirm left ventricular systolic dysfunction (LVSD) by EchocardiographyRadionuclide ventriculography, or Radiological left ventricular angiography,Drug therapy,ST

10、EP 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 NYHA class II-III, unless these are contra-indicated,Drug

11、therapy,STEP 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

12、 low dose and then up-titrate, check tolerability and blood chemistry.,Co-operative North Scandinavian Enalapril Survival Study I– CONSENSUS I N Engl J Med 1987; 316:1429–1435,Studies of Left Ventricular Dysfunction

13、– SOLVD (Treatment Study) SOLVD Investigators N Engl J Med 1991; 325:293–302,,,N Engl J Med 2003; 349: 1893–1906,VALIANT: Results,,,N Engl J Med 2003; 349: 1893–1906,VALIANT: Adverse events,United States Carvedilol Progr

14、am (USCP) Packer M et al. N Engl J Med 1996; 334:1349–1355,Cardiac Insufficiency Bisoprolol Study II (CIBIS II) CIBIS II Investigators, Lancet 1999; 359:9–13,Metoprolol CR/XL Randomized Intervention Trial in Congestive

15、Heart Failure (MERIT-HF) Hjalmarson A et al. Lancet 1999; 353:2001–2007,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 Cardi

16、ol 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 syst

17、olic CHFThey 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,Electrome

18、chanical 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, L

19、VEF <20%,Cardiac resynchronization therapy(biventricular pacing),in appropriately selected patients:improves symptomsimproves exercise performanceimproves QOLimproves long-term morbidity & mortality,,Wang LX.

20、 Exp Clin Cardiol 2003; 7:212.,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 therapyDilated

21、heart failure with EF120 msSinus rhythm,,Future directionsCell-Based TherapiesEmbryonic stem cellsBone marrow cells (contains stem cells and progenitor cells)Circulating blood-derived progenitor cells (EPCs),,Cell-B

22、ased 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 i

23、s still unclear,,Gene TherapyMajor 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 gen

24、e, and sarcoplasmic reticular Ca2+ gene,,Mechanical assistanceCardiac transplantation will always be limited the availability of donor heartsVentricular assist devices (VADs)Mainly used as bridges to transplantationA

25、s destination therapy?REMATCH trial: encouraging but the device was too large with many complications,,Ventricular assist devices (VADs)Current effortReduce the incidence of complications and size of the deviceIndica

26、tions for VADs are expected to expand quickly in the next five years to provide destination therapy,,ConclusionsThe field of HF study is now at a historic junctureThe pandemic of HF is increasing rapidly because of the

27、 aging population and increased number of survival patients following MIStudies on prevention and management of HF is accelerating,,Conclusions (continued)Advances in genetics, cell biology and molecular pharmacology w

28、ill enhance understanding of the causes of HFCurrently used ACEI, beta-blockers and CRT have clear benefits to clinical outcomes of HFDevelopment in bioengineering could have an enormous beneficial impact on both incid

29、ence and management,,Chronic heart failure (CHF),Definitiona complex clinical syndrome with typical clinical symptoms that can occur at rest or on effort, and is characterised by objective evidence of an underlying stru

30、ctural abnormality or cardiac dysfunction that impairs the ventricle to fill with or eject bloodThe term congestive heart failure is no longer used.,MADIT-II,Moss AJ. N Engl J Med. 2002;346:877-83.,,,,,,,,,,,,,,,,Defibr

31、illator,Conventional,P = 0.007,1.0,0.9,0.8,0.7,0.6,0.0,,,Probability of Survival,0,1,2,3,4,Year,No. At RiskDefibrillator742502 (0.91)274 (0.94)110 (0.78)9Conventional 490329 (0.90)170 (0.78) 65 (0.69)3,,Non

32、-pharmacologicalPhysical activity tailored to individualsWalkSlow walking at home 10-30 min a day, 7 days a weekClass IV patients require gentle mobilisation as symptoms allowBed rest for those with acute deteriorat

33、ion of symptoms,,Non-pharmacologicalSodium restriction<3 g sodium/dayNo more than 2 L fluid intake per dayDaily weighingWeight variation should be <2 kg in two consecutive days,Katz, A. M. Circ Heart Fail 20