上海交通大学医学院.ppt

Heart Failure 上海交通大学医学院 附属仁济医院心内科 张 清 副教授 Heart Failure _ZhangQing nHeart failure is the pathophysiological state in which the heart is unable to pump sufficient blood to satisfy the metabolic demands of the body with enough preload. Heart Failure _ZhangQing The Progressive Development of Cardiovascular Disease Endstage Heart DiseaseEndstage Heart Disease Congestive Heart FailureCongestive Heart Failure Ventricular DilationVentricular Dilation RemodelingRemodeling Arrhythmia 314:1547 NITRATES SURVIVAL 06121824303642 Heart Failure _ZhangQing NITRATES TOLERANCE Can be avoided or minimized - Intermittent administration - Use the lowest possible dose Heart Failure _ZhangQing NITRATES CONTRAINDICATIONS Previous hypersensitivity Hypotension ( 80 mmHg) AMI with low ventricular filling pressure 1st trimester of pregnancy WITH CAUTION: Constrictive pericarditis Intracranial hypertension Hypertrophic cardiomyopathy Heart Failure _ZhangQing NITRATES CLINICAL USES Pulmonary congestion Orthopnea and paroxysmal nocturnal dyspnea CHF with myocardial ischemia In acute CHF and pulmonary edema: NTG s.l. or i.v. Heart Failure _ZhangQing VASOCONSTRICTIONVASODILATATION Kininogen Kallikrein Inactive Fragments Angiotensinogen Angiotensin I RENIN Kininase II Inhibitor ALDOSTERONE SYMPATHETIC VASOPRESSIN PROSTAGLANDINS tPA ANGIOTENSIN II BRADYKININ ACE-i. Mechanism of Action A.C.E. Heart Failure _ZhangQing ACEI HEMODYNAMIC EFFECTS Arteriovenous Vasodilatation - PAD, PCWP and LVEDP -SVR and BP -CO and exercise tolerance No change in HR / contractility Renal, coronary and cerebral flow Heart Failure _ZhangQing 75 95 No Additional Treatment Necessary (%) Quinapril Heart Failure Trial JACC 1993;22:1557 ACEI FUNCTIONAL CAPACITY Quinapril continued n=114 Quinapril stopped Placebo n=110 p0.001 100 90 85 80 Weeks Class II-III 16 12621048182014 Heart Failure _ZhangQing ACEI ADVANTAGES Inhibit LV remodeling post-MI Modify the progression of chronic CHF - Survival - Hospitalizations - Improve the quality of life In contrast to others vasodilators, do not produce neurohormonal activation or reflex tachycardia Heart Failure _ZhangQing Placebo Enalapril 12111098765 PROBABILITY OF DEATH MONTHS 0.1 0.8 0 0.2 0.3 0.7 0.4 0.5 0.6 p 0.001 p 0.002 CONSENSUS N Engl J Med 1987;316:1429 ACEI SURVIVAL 43210 Heart Failure _ZhangQing 50 40 30 20 10 0 Months 0612 p = 0.30 241830364248 Enalapril n=2111 Placebo n=2117 SOLVD (Prevention) N Engl J Med 1992;327:685 MORTALITY % ACEI SURVIVAL n = 4228 No CHF symptoms EF 35 Heart Failure _ZhangQing 50 40 30 20 10 0 Months 0612 p = 0.0036 MORTALITY % 2418303642 48 Enalapril n=1285 Placebo n=1284 SOLVD (Treatment) N Engl J M 1991;325:293 ACEI SURVIVAL n = 2589 CHF - NYHA II-III - EF 35 Heart Failure _ZhangQing Mortality % 4 SAVE N Engl J Med 1992;327:669 Years 30 20 10 0 123 Placebo Captopril 0 n=1115 n=1116 p=0.019 -19% ACEI SURVIVAL n = 2231 3 - 16 days post AMI EF 40 12.5 - 150 mg / day Asymptomatic ventricular dysfunction post MI Heart Failure _ZhangQing ISIS-4 GISSI-3 SAVE SMILE AIRE ACEIBenefit Pt Selection Captopril Lisinopril Captopril Zofenopril Ramipril 0.5 / 5 wk 0.8 / 6 wk 4.2 / 3.5 yr 4.1 / 1 yr 6 / 1 yr All with AMI All with AMI EF 40 asymptomatic Ant. AMI, No TRL Clinical CHF TRACE Trandolapril7.6 / 3 yr Vent Dysfx / Clinical CHF EF 35 ACEI SURVIVAL POST MI Heart Failure _ZhangQing ACEI INDICATIONS Clinical cardiac insufficiency - All patients Asymptomatic ventricular dysfunction - LVEF 35 % Heart Failure _ZhangQing ACEI UNDESIRABLE EFFECTS Inherent in their mechanism of action - Hypotension - Hyperkalemia - Angioneurotic edema - Dry cough - Renal Insuff. Heart Failure _ZhangQing ACEI CONTRAINDICATIONS Renal artery stenosis Renal insufficiency Hyperkalemia Arterial hypotension Intolerance (due to side effects) Heart Failure _ZhangQing ANGIOTENSIN II INHIBITORS （ARB) MECHANISM OF ACTION RENIN AngiotensinogenAngiotensin I ANGIOTENSIN II ACE Other paths VasoconstrictionProliferative Action Vasodilatation Antiproliferative Action AT1 AT2 AT1 RECEPTOR BLOCKERS RECEPTORS Heart Failure _ZhangQing AT1 RECEPTOR BLOCKERS DRUGS Losartan Valsartan Irbersartan Candersartan Competitive and selective blocking of AT1 receptors Heart Failure _ZhangQing ALDOSTERONE Retention Na+ Retention H2O Excretion K+ Excretion Mg2+ Collagen deposition Fibrosis - myocardium - vessels Spironolactone Edema Arrhythmias Competitive antagonist of the aldosterone receptor (myocardium, arterial walls, kidney) ALDOSTERONE INHIBITORS Heart Failure _ZhangQing ALDOSTERONE INHIBITORS INDICATIONS FOR DIURETIC EFFECT Pulmonary congestion (dyspnea) Systemic congestion (edema) FOR ELECTROLYTE EFFECTS Hypo K+, Hypo Mg+ Arrhythmias Better than K+ supplements FOR NEUROHORMONAL EFFECTS Please see RALES results, N Engl J Med 1999:341:709-717 Heart Failure _ZhangQing Hyperkalemia Severe renal insufficiency Metabolic acidosis ALDOSTERONE INHIBITORS CONTRAINDICATIONS Heart Failure _ZhangQing -ADRENERGIC BLOCKERS POSSIBLE BENEFICIAL EFFECTS Density of 1 receptors Inhibit cardiotoxicity of catecholamines Neurohormonal activation HR Antihypertensive and antianginal Antiarrhythmic Antioxidant Antiproliferative Heart Failure _ZhangQing BLOCKERS CARVEDILOL 4 studies in U.S.; 1 in Australia/New Zealand U.S. studies with control group Mortality with Placebo8.2% Mortality with Carvedilol2.9% Initial low doses, progressive p 0.0001 Heart Failure _ZhangQing -ADRENERGIC BLOCKERS INDICATIONS and UTILIZATION Begin with very low doses Slow augmentation of dose Slow withdrawal ? Heart Failure _ZhangQing -ADRENERGIC BLOCKERS IDEAL CANDIDATE? Suspected adrenergic activation Arrhythmias Hypertension Angina Heart Failure _ZhangQing -ADRENERGIC BLOCKERS CONTRAINDICATIONS Hypotension: BP 100 mmHg Bradycardia: HR 50 bpm Clinical instability Chronic bronchitis, ASTHMA Severe chronic renal insufficiency Heart Failure _ZhangQing CALCIUM ANTAGONISTS POTENTIAL EFFECTS Antiischemic Peripheral Vasodilatation Inotropy Heart Failure _ZhangQing CALCIUM ANTAGONISTS POSSIBLE UTILITY Diltiazem contraindicated Verapamil and Nifedipine not recommended Vasoselective (amlodipine, nisoldipine), may be useful in ischemia + CHF Heart Failure _ZhangQing ANTICOAGULANTS PREVIOUS EMBOLIC EPISODE ATRIAL FIBRILLATION Identified thrombus LV Aneurysm (3-6 mo post MI) Class III-IV in the presence of: - EF 30 - Aneurysm or very dilated LV Heart Failure _ZhangQing ANTIARRHYTHMICS Sustained VT, with/without symptoms - Blockers - Amiodarone Sudden death from VF - Consider implantable defibrillator Heart Failure _ZhangQing Intractable heart failure n1.To find induction factors n2.To use better doses of drug n3.IABP in severe coronary heart disease erventional treatment for coronary heart disease n5.CABG for severe heart disease n6.heart transplantation Heart Failure _ZhangQing Acute Left Heart Failure nCauses: extensive acute myocardial infarction;acute myocarditis;malignant or accelerated hypertension;mitral stenosis;severe cardiac arrhythmias;rapid and excessive volume injection Heart Failure _ZhangQing Diagnosis nAccording to clinical manifestation:sudden onset orthopnea,coughs,cyanosis ,moist ralse is prominent and wheezing may be heard all over the chest, rapid pulse and weakness. 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