【正文】 Overview of congestive heart failure Congestive heart failure (CHF) is a condition in which the heart is unable to pump sufficient blood to meet the needs of body. CHF can be increased workload imposed on the heart. CHF is acpanied by abnormal increases in blood volume and interstitial fluid。 the heart, veins, and capillaries are therefore generally dilated with blood. Hence the term “congestive(充血性 )” heart failure, since the symptoms include pulmonary congestion with life heart failure, and peripheral edema with right heart failure. Underlying causes of CHF include arteriosclerotic heart disease, hypertensive heart disease, valvular heart disease(心瓣膜病 ), dilated cardiomyopathy(擴張性心肌病 ), and congenital heart disease(先天性心臟病 ). Left systolic dysfunction secondary to coronaryartery disease is the most mon cause of heart failure. Treatment of congestive heart failure Heart Failure ? Final mon pathway for many cardiovascular diseases whose natural history results in symptomatic or asymptomatic left ventricular dysfunction ? Cardinal manifestations of heart failure include dyspnea, fatigue and fluid retention ? Risk of death is 510% annually in patients with mild symptoms and increases to as high as 3040% annually in patients with advanced disease Main causes ? Coronary artery disease ? Hypertension ? Valvular heart disease (心瓣膜病 ) ? Cardiomyopathy (心肌病 ) ? Cor pulmonale Compensatory changes in heart failure ? Activation of SNS ? Activation of RAS ? Increased heart rate ? Release of ADH ? Release of atrial natriuretic peptide心鈉素 ? Chamber enlargement 心室腔擴大 ? Myocardial hypertrophy 心室肥厚 Classification of heart failure ? Class I: No limitation of physical activity ? Class II: Slight limitation of physical activity ? Class III: Marked limitation of physical activity ? Class IV: Unable to carry out physical activity without disfort New classification of heart failure ? Stage A: Asymptomatic with no heart damage but have risk factors for heart failure ? Stage B: Asymptomatic but have signs of structural heart damage ? Stage C: Have symptoms and heart damage ? Stage D: End stage disease ACC/AHA guidelines, 2022 心功能障礙 收縮功能 舒張功能 輸出量 神經(jīng)激素 心肌 ?1受體 RAA CA 心縮力 順應性 心肌肥大、重構 鈉水潴留 血容量 靜脈淤血 血管收縮 阻抗 順應性 后負荷 血管肥厚、重構 前負荷 抗 RAA系統(tǒng)藥 改善舒張功能藥 正性肌力藥 ?受體阻斷藥 利尿藥 減前負荷藥 減后負荷藥 恢復心血管病理形態(tài)的藥 CHF的病理生理過程及可能治療的環(huán)節(jié) 長期病情 心率 Strategy of treatment of CHF The therapeutic goal for CHF is to increase cardiac output. 1) Inotropic agents that increase the strength of contraction of cardiac muscle 2) PDEI (phosphodiesterase inhibitors) agents that increase cAMP to induce systoles and vasodilatation 3) Calcium sensitizers extracellular fluid volume 4) ? adrenergic agonist 5) ? adrenergic antagonist 6) Vasodilators: Calcium channel blocker 7) Decreasing RAS activity: ACEI and AT1 antagonist 8) Diuretic agents Treatment of congestive heart failure Classification 1 Positive inotropic drugs ? Cardiac glycosides ? βadrenergic agonists (New dopamine receptor agonist) ? phosphodiesterase inhibitors ? Calcium sensitizers 2 Diuretics 3 Vasodilators ? Calcium channel blocker ? Nitrylvasodilators ? Hydralazine 4 RAAS inhibitors: antiotensin converting enzyme inhibitor and AT1 antagonist 5 βreceptor blocker Classification1 Positive inotropic drugs Cardiac glycosides/強心苷類 structureactivity relationship A cardiac glycoside molecule consists of an aglycone苷元 or genin配基 , which possesses the same pharmacologic activity as the whole molecule bined chemically with one or more sugars. Cardiac glycosides O O OH CH3 CH3 H O C18 H31O9 12 A C B D 17 3 Digitoxin Digoxin = H at 12 C = OH at 12 C Sugars 3 mols. of digitoxose 3分子洋地黃毒糖 Aglycones 苷元 Unsaturated lactone 不飽和內(nèi)酯環(huán) steroid nucleus 甾核 Convey the pharmacological activity