【正文】 bolism, ? Congestive hepatomegaly, ? Ascites, ? Hepatic sclerosis, ? Imbalance of electrolytes Heart Failure _ZhangQing Laboratory Finding ? Venous pressure:elevated ? Chest roentgenogram:cardiothoracic ratio,pulmonary edema— Kerley’s lines,perivascular and subpleural edema (butterfly and pleural effusion) ? Invasive assessment of cardiac function: ventricular pressure,PCWP, ? Echo and radionuclide Heart Failure _ZhangQing Heart Failure _ZhangQing Heart Failure _ZhangQing Diagnosis and differential diagnosis ? Left heart failure: Symptoms: orthopnea and paroxysmal nocturnal dyspnea Signs: moist and fine crepitant rales, PCWP25mmHg ? Right heart failure: Symptoms: anorexia ,nausea,a sense of fullness after meals and constipation Signs: peripheral edema,congestive heptomegaly,hepatojugular reflux,ascites Heart Failure _ZhangQing Differential diagnosis Differentiation between cardiac and pulmonary dyspnea: ? Chronic obstructive lung disease is usually associated with sputum production,the dyspnea is relieved after patients rid themselves of secretions by coughing rather than specifically by sitting up ? Acute cardiac asthma (paroxysmal nocturnal dyspnea with prominent wheezing) usually occurs in patients who have obvious clinical evidence of heart disease ? Airway obstruction and dyspnea that respond to bronchodilators or smoking cessation favor a pulmonary origin of the dyspnea, while the response of these manifestations to diuretics supports heart failure as the cause of dyspnea Heart Failure _ZhangQing Heart Failure _ZhangQing Therapy ? To get rid of induction factors and plication ? Uses of inotropic agents:digitalis,dobutamine ? Uses of diuretics ? Uses of vasodilators ? Other treatment: sedative drug and oxygen supply Heart Failure _ZhangQing Survival Morbidity Exercise capacity Quality of life Neurohormonal changes Progression of CHF Symptoms TREATMENT OBJECTIVES Heart Failure _ZhangQing TREATMENT Correction of aggravating factors MEDICATIONS Endocarditis Obesity Hypertension Physical activity Dietary excess Pregnancy Arrhythmias (AF) Infections Hyperthyroidism Thromboembolism Heart Failure _ZhangQing TREATMENT PHARMACOLOGIC THERAPY DIURETICS INOTROPES VASODILATORS NEUROHORMONAL ANTAGONISTS OTHERS (Anticoagulants, antiarrhythmics, etc) Heart Failure _ZhangQing PHARMACOLOGIC THERAPY DIURETICS Improved symptoms Decreased mortality Prevention of CHF yes ? ? Vasodil.(Nitrates) yes yes ? DIGOXIN yes = minimal INOTROPES yes mort. ? Other neurohormonal control drugs yes + / ? ACEI yes YES yes Neurohumoral Control NO yes no no YES YES Heart Failure _ZhangQing TREATMENT Normal Asymptomatic LV dysfunction EF 40% Symptomatic CHF NYHA II Inotropes Specialized therapy Transplant Symptomatic CHF NYHA IV Symptomatic CHF NYHA III Secondary prevention Modification of physical activity ACEI Diuretics mild Neurohormonal inhibitors Digoxin? Loop Diuretics Heart Failure _ZhangQing Cortex Medulla Thiazides Inhibit active exchange of ClNa in the cortical diluting segment of the ascending loop of Henle Ksparing Inhibit reabsorption of Na in the distal convoluted and collecting tubule Loop diuretics Inhibit exchange of ClNaK in the thick segment of the ascending loop of Henle Loop of Henle Collecting tubule DIURETICS Heart Failure _ZhangQing THIAZIDES MECHANISM OF ACTION Excrete 5 10% of filtered Na+ Elimination of K Inhibit carbonic anhydrase: increase elimination of HCO3 Excretion of uric acid, Ca and Mg No dose effect relationship Heart Failure _ZhangQing LOOP DIURETICS MECHANISM OF ACTION Excrete 15 20% of filtered Na+ Elimination of K+, Ca+ and Mg++ Resistance of afferent arterioles Cortical flow and GFR Release renal PGs NSAIDs may antagonize diuresis Heart Failure _ZhangQing KSPARING DIURETICS MECHANISM OF ACTION Eliminate 5% of filtered Na+ Inhibit exchange of Na+ for K+ or H+ Spironolactone = petitive antagonist for the aldosterone receptor Amiloride and triamterene block Na+ channels controlled by aldosterone Heart Failure _ZhangQing Volume and preload Improve symptoms of congestion No direct effect on CO, but excessive preload reduction may Improves arterial distensibility Neurohormonal activatio Levels of NA, Ang II and ARP Exception: with spironolactone DIURETIC EFFECTS Heart Failure _ZhangQing DIURETICS ADVERSE REACTIONS Thiazide and Loop Diuretics Changes in electrolytes: Volume Na+, K+, Ca++, Mg++ metabolic alkalosis Metabolic changes: glycemia, uremia, gout LDLC and TG Cutaneous allergic reactions Heart Failure _ZhangQing DIURETICS ADVERSE REACTIONS KSPARING DIURETICS Changes in electrolytes Na+, K+, acidosis Musculoskeletal: Cramps, weakness Cutaneous allergic reactions : Heart Failure _ZhangQing Na+ K+ K+ Na+ Na+ Ca++ Ca++ NaK ATPase NaCa Exchange Myofilaments DIGOXIN CONTRACTILITY Heart Failure _ZhangQing DIGOXIN PHARMACOKINETIC PROPERTIES Oral absorption (%) Protein binding (%) Volume of distribution (l/Kg) Half life Elimination Onset (min) . oral Maximal effect (h) . oral Duration Therapeutic level (ng/ml) 60 75 25 6 (39) 36 (2646) h Renal 5 30 30 90 2 4 3 6 2 6 days 2 Heart Failure _ZhangQing DIGOXIN DIGITALIZATION STRATEGIES (mg) / d / d + / 4 h ILD: oral 1224 h + / 6 h oral 25 d / 612 h Loading dose (mg) Maintenance Dose ILD = average INITIAL dose required for digox