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1、Management of Heart Failure: Past, Present and Future,Lexin Wang, M.D., Ph.D., FCSANZ Professor of Clinical Pharmacology Head, Cardiovascular Research,Objectives,History and pathogenesis Epidemiology and risk factors Current management Future directions,Katz, A. M. Circ Heart Fail 2008;1:63-71,Willi
2、am 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. Epigenetics (实验胚胎学),Katz, A. M. Circ Heart
3、 Fail 2008;1:63-71,Changing management of heart failure over the past 40 years,CHF-Prevalence,Approximately 5.5 million 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,CHF pr
4、evalence- 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 the country,Age-related prevalence of CHF,American National HF project 34,587 hospitalized patients,Age (median, yrs)
5、 73 Gender (female, %) 59% History (%) hypertension 61% coronary artery disease 56% diabetes 38% COPD 33% atrial fibrillation 30% Havranek EP et al. Am Heart J 2002;143:412-417,Classification of CHF,Systolic CHF Weakened ability of the ventricles to contract Heart failure with preserved systolic fun
6、ction Impaired diastolic filling of the left ventricle, resulting in high filling pressure, with or without systolic dysfunction Accounts 40% of all CHF,Management of CHF,Life style changes Pharmacological Surgical Devices CABG, PCI Cardiac transplantation,Drug therapy,STEP 1 Confirm left ventricula
7、r 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 LVSD with a diuretic and an ACE inhibitor for NYHA class I-IV, and a beta-blocker fo
8、r NYHA class II-III, unless these are contra-indicated,Drug 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 Initiate spironolactone first followed by digoxin, both at a low dose and then u
9、p-titrate, check tolerability and blood chemistry.,Co-operative North Scandinavian Enalapril Survival Study I CONSENSUS I N Engl J Med 1987; 316:14291435,Studies of Left Ventricular Dysfunction SOLVD (Treatment Study) SOLVD Investigators N Engl J Med 1991; 325:293302,N Engl J Med 2003; 349: 18931906
10、,VALIANT: Results,N Engl J Med 2003; 349: 18931906,VALIANT: Adverse events,United States Carvedilol Program (USCP) Packer M et al. N Engl J Med 1996; 334:13491355,Cardiac Insufficiency Bisoprolol Study II (CIBIS II) CIBIS II Investigators, Lancet 1999; 359:913,Metoprolol CR/XL Randomized Interventio
11、n Trial in Congestive Heart Failure (MERIT-HF) Hjalmarson A et al. Lancet 1999; 353:20012007,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 Cardiol 2007;49:963-971,Death After a Nonfatal Myocardial Infarct
12、ion or Nonfatal Stroke,CCBs: 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 blockers such as verapamil and
13、 diltiazem are contraindicated in patients with systolic heart failure,Electromechanical 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
14、VEF 20%,Cardiac resynchronization therapy (biventricular pacing),in appropriately selected patients: improves symptoms improves exercise performance improves QOL improves long-term morbidity & mortality,Wang LX. Exp Clin Cardiol 2003; 7:212.,TABLE 2. Risk of Sudden Cardiac Death,Risk of Sudden Cardi
15、ac Death,Saxon LA et al. Circulation. 2006;114:2766-72.,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) Circulati
16、ng blood-derived progenitor cells (EPCs),Cell-Based Therapies 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 Majo
17、r challenges Development of an ideal vector (e.g. adenovirus) 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 a
18、vailability of donor hearts Ventricular assist devices (VADs) Mainly 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 s
19、ize of the device Indications for VADs are expected to expand quickly 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 patien
20、ts following MI Studies on prevention and management of HF is accelerating,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 De
21、velopment in bioengineering could have an enormous beneficial impact on both incidence and management,Chronic 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 str
22、uctural abnormality or cardiac dysfunction that impairs the ventricle to fill with or eject blood The term congestive heart failure is no longer used.,MADIT-II,Moss AJ. N Engl J Med. 2002;346:877-83.,Defibrillator,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,
23、No. At Risk Defibrillator 742 502 (0.91) 274 (0.94) 110 (0.78) 9 Conventional 490 329 (0.90) 170 (0.78) 65 (0.69) 3,Non-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 B
24、ed rest for those with acute deterioration of symptoms,Non-pharmacological Sodium restriction 3 g sodium/day No more than 2 L fluid intake per day Daily weighing Weight variation should be 2 kg in two consecutive days,Katz, A. M. Circ Heart Fail 2008;1:63-71,Two views of the circulation,Starling curve,Katz, A. M. Circ Heart Fail 2008;1:63-71,Proliferative signaling pathways that mediate cardiac hypertrophy,