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HEART FAILURE: CONGESTIVE CARDIAC FAILURE
- 1. Congestive Cardiac Failure Dr.R. Senthil Kumar
- 2. Introduction to HeartFailure • Heart unable to provide adequate perfusion of peripheral organs to meet their metabolic requirements • Characterized by: 1. Reduction in cardiac output 2. Increased TPR • Progressing to congestive heart failure (CHF) is accompanied by peripheral and pulmonary edema.
- 3. Recent Advances VsReality • Major advances in recent years in management of patients with CHF • In 2000 an estimated 4.7 million people in the United States had HF • The median survival after initial diagnosis is 1.7 years for men and 3.2 years for women. • Sudden cardiac death is common in patients with heart failure, contributing to 50% of all 287,000 deaths in the United States last year
- 4. Acute Vs ChronicHF • In a patient with acute heart failure, the short-term aim is stabilization by providing symptomatic treatment through intravenous interventions. • Management of chronic heart failure is multifaceted, with the long-term aims of: • relieving symptoms • improving hemodynamics • improving quality of life and • decrease mortality.
- 5. Cardiac Vs Noncardiactargets • Conventional belief that the primary defect in HF is in the heart • Reality is that HF involves many other processes and organs • Research has shown that therapy directed at noncardiac targets are more valuable than cardiac targets
- 6. Compensation in HF •Heart failure is usually accompanied by an increase in: 1. Sympathetic nervous system (SNS) 2. Chronic up-regulation of the renin- angiotensin-aldosterone system (RAAS) and effects of aldosterone on heart, vessels, and kidneys. • CHF should be viewed as a complex, interrelated sequence of events involving hemodynamic, and neurohormonal events.
- 7. Compensation contd.. • Ina failing heart, the loss of contractile function leads to a decline in CO and a decrease in arterial BP. • Baroreceptors sense the hemodynamic changes and initiate countermeasures to maintain support of the circulatory system. • Activation of the SNS serves as a compensatory mechanism in response to the earlier • This helps maintain adequate cardiac output by: 1. Increasing myocardial contractility and heart rate (β1- adrenergic receptors) 2. Increasing vasomotor tone (α1-adrenergic receptors) to maintain systemic blood pressure
- 8. Consequences of hyperadrenergic state •Over the long term, this hyperadrenergic state leads to irreversible myocyte damage, cell death, and fibrosis. • In addition, the augmentation in peripheral vasomotor tone increases LV afterload • This places an added stress upon the left ventricle and an increase in myocardial O2 demand (ventricular remodeling). • The frequency and severity of cardiac arrhythmias are enhanced in the failing heart
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- 11. Therapeutic Overview Problem • Reducedforce of contraction • Decreased cardiac output • Increased total peripheral resistance • Inadequate organ perfusion • Development of edema • Decreased exercise tolerance • Ischemic heart disease • Sudden death • Ventricular remodeling and decreased function
- 12. Goals and drugtherapy Goals • Alleviation of symptoms, improve quality of life • Arrest ventricular remodeling • Prevent sudden death Nondrug therapy • Reduce cardiac work; rest, weight loss, low Na+ diet Drug therapy • Chronic heart failure • ACE-I, β-blockers, ARB, aldosterone antagonists, digoxin, diuretics • Acute heart failure • Intravenous diuretics, inotropic agents, PDE inhibitors, vasodilator
- 13. Signs and symptoms •Tachycardia • Decreased exercise tolerance & SOB • Peripheral and pulmonary edema • Cardiomegaly
- 15. Diuretics • Bottom line:they decrease fluid volumes • Four Flavours: • Carbonic anhydrase inhibitors • Loop diuretics • Thiazide diuretics • K+-sparing
- 16. Renin angiotensin system •Baroreceptor mediated activation of the SNS leads to an increase in renin release and formation of angiotensin II • Angiotensin II acts through AT1 and AT2 receptors (most of its actions occur through AT1 receptors) • This causes vasoconstriction and stimulates aldosterone production • RAS remains the most important target of chronic CHF therapy
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- 18. MOA • ACE-Inhibitors andARB animation • Blockade of ACE • Decreased AT-II • Decreased aldosterone • Decreased fluid retention • Vasodilation • Reduced preload and afterload • Slows cardiac remodeling
- 19. Advantages • Improves symptomssignificantly • Improves exercise tolerance • Slows progression of the disease • Prolong survival in established cases
- 20. ADR • What arethe ADR of ACEIs? • Cough (why?) • Postural hypotention (why?) • Hyperkalemia (possible Drug interactions?) • Contraindicated in pregnant women (1st trimester) • Rare: angioedema
- 21. Other Vasodilators: • Mechanism2: • Direct smooth muscle relaxants • Nitrates • Venous dilators • Reduce preload • Eg: sodium nitropruside
- 22. Inotropes • Increase forceof contraction • All increase intracellular cardiac Ca++ concentration • Eg: • Digitalis (cardiac glycoside) • Dobutamine (β-adrenergic agonist) • Amrinone (PDE inhibitor)
- 23. Cardiac glycosides • Digitalis •Sourced from foxglove plant • 1785, Dr. William Withering’s monograph on digitalis • Has a profound effect on the cardiac contractility
- 25. Pck • Two drugs(digoxin, digitoxin) • Well absorbed orally • 10% of population have bacteria in the gut, which inactivate digoxin, needing an increased dose in such • Beware of using antibiotics in such patients • Digoxin has a very narrow ther. Margin
- 26. Pck • Taken orally •Enters CNS (so what?) • Renal clearance proportional to CC • To be used with extreme caution in patients suffering from renal impairment
- 27. MOA • Regulation ofcytosolic Ca metabolism: • Reversibly combine with sodium-potassium ATPase of the cardiac cell membrane • Results in inhibition of pump activity • This leads to in intracellular Na conc. • This favors Ca ions in the cell • Ca levels result in increased systolic force of contraction
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- 30. Additional MOA • Forceof contraction resembles to that of the normal heart • Improved circulation leads to reduced sympathetic activity • This reduces PVR • All this leads to reduction in HR • Vagal tone is enhanced • Finally myocardial O2 demand is reduced
- 31. Electrophysiological effects onthe heart Direct Indirect (increased vagal tone) SA Node No effect at therapeutic dose No effect at therapeutic dose Atrial muscle High dose increases rate of spontaneous depolarization High dose decreases rate of spontaneous depolarization AV node Increased refractory period Decreased conduction velocity Decreased conduction velocity Increased refractory period His-Purkinje system Increased refractory period Increased refractory period Decreased conduction velocity Decreased conduction velocity High dose increases triggered activity None Toxic doses enhance pacemaker
- 32. Uses • Severe LVsystolic dysfunction • Only after initiation of diuretics and vasodialtor therapy • Management of patients with chronic atrial fibrillation • Cannot arrest the progression of pathological changes causing heart failure, and does not prolong life in patients with CHF
- 33. ADR • Digitalis toxicityis one among most commonest encountered (why?) • Therapeutic concentration- 0.5-1.5 ng/ml • Often the first step is discontinuation of Rx • Digoxin levels must be monitored closely
- 34. Signs of digoxintoxicity • CNS: Malaise, confusion, depression, vertigo, vision (abnormalities in color vision) • GI: Anorexia, nausea, intestinal cramping, diarrhea • Cardiovascular: Palpitations, syncope, arrhythmias, bradycardia, AV node block, tachycardia
- 35. Factors increasing thepossibility of digoxin toxicity • Pharmacological and toxic effects are greater in hypokalemic patients. • K+-depleting diuretics are a major contributing factor to digoxin toxicity.
- 36. Management Arrhythmias maybe converted to normal sinus rhythm by K+. when the plasma K+ conc. is low or within the normal range. When the plasma K+ conc. is high, antiarrhythmic drugs, such as lidocaine, procainamide, or propranolol, can be used. Severe toxicity treated with Digibind, an anti- digoxin antibody.
- 37. • A 96-year-oldAAF was admitted from a nursing home with complaints of abdominal pain, N/V, dizziness, confusion and double vision for 5 days. She was discharged from the hospital just 4 days ago. Digoxin was started during that previous hospitalization for control of tachycardia in atrial fibrillation. One day prior to discharge, digoxin level was 1.8 mg/mL and digoxin dose was decreased to 125 mcg PO Q 48 hr. PMH Hypertension, atrial fibrillation, coronary artery disease, stroke, congestive heart failure. Medications Metoprolol, Digoxin, ASA, lisinopril, Lasix, Coumadin, Nexium What could it be???
- 38. Dopamine • Dopamine actsat a variety of receptors (dose dependant) • Rapid elimination- can only be administered as a continuous infusion
- 39. Dobutamine • Stimulates beta-adrenergicreceptors and produces a positive inotropic response • Unlike the vasoconstriction seen with high doses of dopamine, dobutamine produces a mild vasodilatation
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- 41. PDE inhibitors • Inamrinone(amrinone) and Milrinone (bipyridines) • Acts by inhibiting the enzyme Phosphodiesterase • Thus lead to increase of intracellular concentrations of cAMP • cAMP is responsible for the conversion of inactive protein kinase to active form • Protein kinases are responsible for phosphorylation of Ca channels • Thus causing increased Ca entry into the cell.
- 42. MOA • Increase myocardialcontractility by increasing the Ca influx during AP • Also have vasodilating effect • Selective for PDE isoenzyme-3 (found in cardiac and smooth muscle)
- 43. Current status • Bothare orally active • Only available in parenteral forms • Limited efficacy • Clinical trials- increased mortality (oral) • Still new drugs are under trial
- 44. ADR • Inamrinone: nausea,vomiting, arrhythmias, thrombocytopenia and liver enzyme changes • Withdrawn in some countries • Milrinone: arrhythmias, less likely to cause other ADR
- 45. (BNP)-Niseritide • Brain (B-type)natriuretic peptide (BNP) is secreted constitutively by ventricular myocytes in response to stretch • BNP binds to receptors in the vasculature, kidney, and other organs, producing potent vasodilation with rapid onset and offset of action by increasing levels of cGMP • Niseritide is recombinant human BNP approved for treatment of acute decompensated CHF.
- 46. BNP contd.. • Itreduces systemic and pulmonary vascular resistances, causing an indirect increase in cardiac output and diuresis. • Effective in HF because cause reduction in preload and afterload • ADR- hypotension
- 47. Beta blockers • Overwhelmingevidence to support the use of β-blockers in CHF, however • Mechanism involved remain unclear • Part of their beneficial effects may derive from slowing of heart rate and decrease myocardial O2consumption. • This would lessen the frequency of ischemic events and potential for development of a lethal arrhythmia.
- 48. Beta blockers • Suggestedmechanisms also include reduced remodeling • β-Blockers may be beneficial through resensitization of the down-regulated receptor, improving myocardial contractility. • Recent studies with bisoprolol, carvedilol and metoprolol showed a reduction in mortality in patients with these drugs • CI in unstable cases
- 49. Management of ChronicHF (combination of drugs) • Limit physical activity • Reduce weight • Reduce water intake • Control HT • Na restriction • Diuretics • ACE-Is • Digitalis (ther. margin, DI with quinidine) • Beta blockers • Vasodilators
- 50. Management of acuteHF • Diuretics • Vasodilators • Inotropic drugs • Life support • Treating cause (surgery to correct valvular disorders)