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1、Management of Heart Failure: Past, Present and FutureLexin Wang, M.D., Ph.D., FCSANZProfessor of Clinical PharmacologyHead, Cardiovascular Research ObjectivesHistory and pathogenesisEpidemiology and risk factorsCurrent managementFuture directionsKatz, A. M. Circ Heart Fail 2008;1:63-71William Harvey
2、, 1628Changing 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 (实验实验胚胎学胚胎学)Katz, A. M. Circ Heart Fail
3、2008;1:63-71Changing management of heart failure over the past 40 yearsCHF-PrevalenceApproximately 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 2004 is US $28.8 billionCHF prevalence- Aus
4、tralia2% of adult populationApproximately 241,000 patients30,000 new cases each year42,000 hospitalisations in 2004-2005Accounts for 0.8% of all hospitalisations in the countryAge-related prevalence of CHF American National HF project 34,587 hospitalized patientsAge (median, yrs)73Gender (female, %)
5、59%History (%)hypertension61%coronary artery disease56%diabetes38%COPD33%atrial fibrillation30% Havranek EP et al. Am Heart J 2002;143:412-417Classification of CHFSystolic CHFWeakened ability of the ventricles to contractHeart failure with preserved systolic functionImpaired diastolic filling of the
6、 left ventricle, resulting in high filling pressure, with or without systolic dysfunctionAccounts 40% of all CHFManagement of CHFLife style changesPharmacologicalSurgicalDevicesCABG, PCICardiac transplantationDrug therapySTEP 1Confirm left ventricular systolic dysfunction (LVSD) by EchocardiographyR
7、adionuclide ventriculography, or Radiological left ventricular angiography Drug 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 NYHA class II-III, unless these are contra-indicated
8、Drug 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 dose and then up-titrate, check tolerability and blood chemistry.Co-opera
9、tive North S Scandinavian Enalapril Survival S Study I CONSENSUS I N Engl J Med 1987; 316:14291435Studies of Left Ventricular Dysfunction SOLVD (Treatment Study) SOLVD Investigators N Engl J Med 1991; 325:293302 N Engl J Med 2003; 349: 18931906VALIANT: ResultsN Engl J Med 2003; 349: 18931906VALIANT:
10、 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 1999; 359:913 Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF) Hjalmarson A
11、 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 After a Nonfatal Myocardial Infarction or Nonfatal StrokeCCBs: NHF recommendationsAmlodipine and f
12、elodipine 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 contraindicated in patients with systolic heart fail
13、ureElectromechanical 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 male, LBBB, LVEF 20%0.550.01(0.35 to 0.87)QRS 160 ms0.630.05(0.40 to 0.997)Female g
14、ender0.470.01(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.Indications for CRT NYHA III-IV, despite optimal medical therapyDilated heart failure w
15、ith EF120 msSinus rhythmFuture directionsCell-Based TherapiesEmbryonic stem cellsBone marrow cells (contains stem cells and progenitor cells)Circulating blood-derived progenitor cells (EPCs)Cell-Based TherapiesSeveral small trials demonstrated improvement of LV functionChallengesCurrent studies aret
16、oo small to assess clinical outcomesMethod of preparation and delivery uncertainThe best type of cells to use is still unclearGene TherapyMajor challengesDevelopment of an ideal vector (e.g. adenovirus)A method of delivery of these vectorsIdentification of appropriate gene targets, e.g. cardiac S100
17、A1, a calcium binding gene, and sarcoplasmic reticular Ca2+ geneMechanical assistanceCardiac transplantation will always be limited the availability of donor heartsVentricular assist devices (VADs)Mainly used as bridges to transplantationAs destination therapy?REMATCH trial: encouraging but the devi
18、ce was too large with many complicationsVentricular assist devices (VADs)Current effortReduce the incidence of complications and size of the deviceIndications for VADs are expected to expand quickly in the next five years to provide destination therapyConclusionsThe field of HF study is now at a his
19、toric junctureThe pandemic of HF is increasing rapidly because of the 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 will enhance un
20、derstanding 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 incidence and managementChronic heart failure (CHF)Definitiona complex clinical syndrome with typical
21、 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 bloodThe term congestive heart failure is no longer used.MADIT-IIMoss AJ. N Engl J Med. 2
22、002;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)3Non-pharmacologicalPhysical activity tailored to individualsWalkSlow walking at home 10-30 min
23、a day, 7 days a weekClass IV patients require gentle mobilisation as symptoms allowBed rest for those with acute deterioration of symptomsNon-pharmacologicalSodium restriction3 g sodium/dayNo more than 2 L fluid intake per dayDaily weighingWeight variation should be 2 kg in two consecutive daysKatz, A. M. Circ Heart Fail 2008;1:63-71Two views of the circulationStarling curveKatz, A. M. Circ Heart Fail 2008;1:63-71Proliferative signaling pathways that mediate cardiac hypertrophy
