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    Congailure Congailure Presentation Transcript

    • Congestive Cardiac Failure Dr. R. Senthil Kumar
    • Introduction to Heart Failure
      • Heart unable to provide adequate perfusion of peripheral organs to meet their metabolic requirements
      • Characterized by:
      • Reduction in cardiac output
      • Increased TPR
        • Progressing to congestive heart failure (CHF) is accompanied by peripheral and pulmonary edema.
    • Recent Advances Vs Reality
      • 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
    • Acute Vs Chronic HF
      • 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.
    • Cardiac Vs Noncardiac targets
      • 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
    • Compensation in HF
      • Heart failure is usually accompanied by an increase in:
      • Sympathetic nervous system (SNS)
      • 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.
    • Compensation contd..
      • In a 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:
      • Increasing myocardial contractility and heart rate (β 1 -adrenergic receptors)
      • Increasing vasomotor tone (α 1 -adrenergic receptors) to maintain systemic blood pressure
    • 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 O 2 demand (ventricular remodeling).
      • The frequency and severity of cardiac arrhythmias are enhanced in the failing heart
      • Figure p.203 kat
    • Pathophysiology
      • CHF pathophysiology animation
    • Therapeutic Overview
      • Problem
      • Reduced force 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
    • Goals and drug therapy
      • 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
    • Signs and symptoms
      • Tachycardia
      • Decreased exercise tolerance & SOB
      • Peripheral and pulmonary edema
      • Cardiomegaly
    • Diuretics
      • Bottom line: they decrease fluid volumes
      • Four Flavours:
        • Carbonic anhydrase inhibitors
        • Loop diuretics
        • Thiazide diuretics
        • K + -sparing
    • 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 AT 1 and AT 2 receptors (most of its actions occur through AT 1 receptors)
      • This causes vasoconstriction and stimulates aldosterone production
      • RAS remains the most important target of chronic CHF therapy
    • Effects of AT-II
    • MOA
      • ACE-Inhibitors and ARB animation
      • Blockade of ACE
      • Decreased AT-II
      • Decreased aldosterone
      • Decreased fluid retention
      • Vasodilation
      • Reduced preload and afterload
      • Slows cardiac remodeling
    • Advantages
      • Improves symptoms significantly
      • Improves exercise tolerance
      • Slows progression of the disease
      • Prolong survival in established cases
    • ADR
      • What are the ADR of ACEIs?
      • Cough (why?)
      • Postural hypotention (why?)
      • Hyperkalemia (possible Drug interactions?)
      • Contraindicated in pregnant women (1 st trimester)
      • Rare: angioedema
    • Other Vasodilators:
      • Mechanism 2:
        • Direct smooth muscle relaxants
        • Nitrates
          • Venous dilators
          • Reduce preload
          • Eg: sodium nitropruside
    • Inotropes
      • Increase force of contraction
      • All increase intracellular cardiac Ca ++ concentration
      • Eg:
        • Digitalis (cardiac glycoside)
        • Dobutamine ( β -adrenergic agonist)
        • Amrinone (PDE inhibitor)
    • Cardiac glycosides
      • Digitalis
      • Sourced from foxglove plant
      • 1785, Dr. William Withering’s monograph on digitalis
      • Has a profound effect on the cardiac contractility
    • 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
    • Pck
      • Taken orally
      • Enters CNS (so what?)
      • Renal clearance proportional to CC
      • To be used with extreme caution in patients suffering from renal impairment
    • MOA
      • Regulation of cytosolic 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
    • Digoxin MOA
    • Na/K ATPase inhibition
    • Additional MOA
      • Force of 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 O 2 demand is reduced
    • Electrophysiological effects on the heart
    • Uses
      • Severe LV systolic 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
    • ADR
      • Digitalis toxicity is 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
    • Signs of digoxin toxicity
      • 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
    • Factors increasing the possibility of digoxin toxicity
      • Pharmacological and toxic effects are greater in hypokalemic patients.
      • K + -depleting diuretics are a major contributing factor to digoxin toxicity.
    • Management
      • Arrhythmias may be 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.
      • A 96-year-old AAF 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???
    • Dopamine
      • Dopamine acts at a variety of receptors (dose dependant)
      • Rapid elimination- can only be administered as a continuous infusion
    • Dobutamine
      • Stimulates beta-adrenergic receptors and produces a positive inotropic response
      • Unlike the vasoconstriction seen with high doses of dopamine, dobutamine produces a mild vasodilatation
    • MOA
    • 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.
    • MOA
      • Increase myocardial contractility by increasing the Ca influx during AP
      • Also have vasodilating effect
      • Selective for PDE isoenzyme-3 (found in cardiac and smooth muscle)
    • Current status
      • Both are orally active
      • Only available in parenteral forms
      • Limited efficacy
      • Clinical trials- increased mortality (oral)
      • Still new drugs are under trial
    • ADR
      • Inamrinone: nausea, vomiting, arrhythmias, thrombocytopenia and liver enzyme changes
      • Withdrawn in some countries
      • Milrinone: arrhythmias, less likely to cause other ADR
    • (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.
    • BNP contd..
      • It reduces 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
    • Beta blockers
      • Overwhelming evidence 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 O 2 consumption.
      • This would lessen the frequency of ischemic events and potential for development of a lethal arrhythmia.
    • Beta blockers
      • Suggested mechanisms 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
    • Management of Chronic HF (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
    • Management of acute HF
      • Diuretics
      • Vasodilators
      • Inotropic drugs
      • Life support
      • Treating cause (surgery to correct valvular disorders)