【文章內(nèi)容簡介】 in loading Heart Failure _ZhangQing DIGOXIN HEMODYNAMIC EFFECTS Cardiac output LV ejection fraction LVEDP Exercise tolerance Natriuresis Neurohormonal activation Heart Failure _ZhangQing DIGOXIN NEUROHORMONAL EFFECTS Plasma Noradrenaline Peripheral nervous system activity RAAS activity Vagal tone Heart Failure _ZhangQing WORSENING OF CHF % p = DIGOXIN: mg /d ( ng/ml) EF 35% Class IIII (digoxin+diuretic+ACEI) Also significantly decreased exercise time and LVEF. DIGOXIN EFFECT ON CHF PROGRESSION RADIANCE N Engl J Med 1993。329:1 Placebo n=93 DIGOXIN Withdrawal DIGOXIN n=85 30 10 0 20 100 80 20 0 40 60 Days Heart Failure _ZhangQing 50 40 30 20 10 0 Placebo n=3403 DIGOXIN n=3397 48 0 12 24 36 OVERALL MORTALITY % DIG N Engl J Med 1997。336:525 Months p = Heart Failure _ZhangQing DIGOXIN LONG TERM EFFECTS Survival similar to placebo Fewer hospital admissions More serious arrhythmias More myocardial infarctions Heart Failure _ZhangQing DIGOXIN CLINICAL USES AF with rapid ventricular response CHF refractory to other drugs Other indications? Can be bined with other drugs Heart Failure _ZhangQing DIGOXIN CONTRAINDICATIONS ABSOLUTE: Digoxin toxicity RELATIVE Advanced AV block without pacemaker Bradycardia or sick sinus without PM PVC’s and TV Marked hypokalemia WPW with atrial fibrillation Heart Failure _ZhangQing DIGOXIN TOXICITY CARDIAC MANIFESTATIONS ARRHYTHMIAS : Ventricular (PVCs, TV, VF) Supraventricular (PACs, SVT) BLOCKS: SA and AV blocks CHF EXACERBATION Heart Failure _ZhangQing DIGOXIN TOXICITY EXTRACARDIAC MANIFESTATIONS GASTROINTESTINAL: Nausea, vomiting, diarrhea NERVOUS: Depression, disorientation, paresthesias VISUAL: Blurred vision, scotomas and yellowgreen vision Heart Failure _ZhangQing CARDIAC GLYCOSIDES SYMPATHOMIMETICS Catecholamines 223。adrenergic agonists PHOSPHODIESTERASE INHIBITORS Amrinone Enoximone Others Milrinone Piroximone POSITIVE INOTROPES Heart Failure _ZhangQing 223。ADRENERGIC STIMULANTS CLASSIFICATION B1 Stimulants Increase contractility Dobutamine Doxaminol Xamoterol Butopamine Prenalterol Tazolol B2 Stimulants Produce arterial vasodilatation and reduce SVR Pirbuterol Carbuterol Rimiterol Fenoterol Tretoquinol Salbutamol Terbutaline Salmefamol Soterenol Quinterenol Mixed Dopamine Heart Failure _ZhangQing DOPAMINE AND DOBUTAMINE EFFECTS Receptors Contractility Heart Rate Arterial Press. Renal perfusion Arrhythmia DA (181。g / Kg / min) Dobutamine 2 DA1 / DA2 177。 177。 177。 ++ 2 5 223。1 ++ + + + 177。 5 223。1 + a ++ ++ ++ 177。 ++ 223。1 ++ 177。 ++ + 177。 Heart Failure _ZhangQing POSITIVE INOTROPES CONCLUSIONS May increase mortality Safer in lower doses Use only in refractory CHF NOT for use as chronic therapy Heart Failure _ZhangQing Venous Vasodilatation MIXED Calcium antagonists aadrenergic Blockers ACEI Angiotensin II inhibitors K+ channel activators Nitroprusside VENOUS Nitrates Molsidomine ARTERIAL Minoxidil Hydralazine VASODILATORS CLASSIFICATION Arterial Vasodilatation Heart Failure _ZhangQing 1 VENOUS VASODILATATION Preload 2 Coronary vasodilatation Myocardial perfusion 3 Arterial vasodilatation Afterload 4 Others Pulmonary congestion Ventricular size Vent. Wall stress MVO2 NITRATES HEMODYNAMIC EFFECTS ? Cardiac output ? Blood pressure Heart Failure _ZhangQing PROBABILITY OF DEATH 0 Placebo (273) Prazosin (183) Hz + ISDN (186) MONTHS VHefT1 N Engl J Med 1986。314:1547 NITRATES SURVIVAL 0 6 12 18 24 30 36 42 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 . or . Heart Failure _ZhangQing VASOCONSTRICTION VASODILATATION Kininogen Kallikrein Inactive Fragments Angiotensinogen Angiotensin I RENIN Kininase II Inhibitor ALDOSTERONE SYMPATHETIC VASOPRESSIN PROSTAGLANDINS tPA ANGIOTENSIN II BRADYKININ ACEi. Mechanism of Action . 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 p 100 90 85 80 Weeks Class IIIII 16 12 6 2 10 4 8 18 20 14 Heart Failure _ZhangQing ACEI ADVANTAGES Inhibit LV remodeling postMI 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 Ena