530 likes | 994 Views
Introduction to Heart Failure. Heart unable to provide adequate perfusion of peripheral organs to meet their metabolic requirementsCharacterized by:Reduction in cardiac outputIncreased TPRProgressing to congestive heart failure (CHF) is accompanied by peripheral and pulmonary edema. . Recent Ad
E N D
1. Congestive Cardiac Failure Dr. R. Senthil Kumar
2. 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.
3. 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
4. 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.
5. 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
6. 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.
7. 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 (ß1-adrenergic receptors)
Increasing vasomotor tone (a1-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
9. Figure p.203 kat
10. Pathophysiology CHF pathophysiology animation
11. 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
12. 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, ß-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
17. Effects of AT-II
18. 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
19. Advantages Improves symptoms significantly
Improves exercise tolerance
Slows progression of the disease
Prolong survival in established cases
20. ADR What are the ADR of ACEIs?
Cough (why?)
Postural hypotention (why?)
Hyperkalemia (possible Drug interactions?)
Contraindicated in pregnant women (1st trimester)
Rare: angioedema
21. Other Vasodilators: Mechanism 2:
Direct smooth muscle relaxants
Nitrates
Venous dilators
Reduce preload
Eg: sodium nitropruside
22. Inotropes Increase force of contraction
All increase intracellular cardiac Ca++ concentration
Eg:
Digitalis (cardiac glycoside)
Dobutamine (ß-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 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
28. Digoxin MOA
29. Na/K ATPase inhibition
30. 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 O2 demand is reduced
31. Electrophysiological effects on the heart
32. 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
33. 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
34. 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
35. 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.
36. 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.
37. 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.PMHHypertension, atrial fibrillation, coronary artery disease, stroke, congestive heart failure.MedicationsMetoprolol, Digoxin, ASA, lisinopril, Lasix, Coumadin, Nexium What could it be???
38. Dopamine Dopamine acts at a variety of receptors (dose dependant)
Rapid elimination- can only be administered as a continuous infusion
39. 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
40. MOA
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 myocardial contractility 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 Both are 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.. 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
47. Beta blockers Overwhelming evidence to support the use of ß-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 Suggested mechanisms also include reduced remodeling
ß-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 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
50. Management of acute HF Diuretics
Vasodilators
Inotropic drugs
Life support
Treating cause (surgery to correct valvular disorders)