congestive heart failure.pptx, heart failure

ppt discussing congestive heart failure

1. HEART FAILURE PROF. SANJAY KHATTRI PROFESSOR DEPARTMENT OF PHARMACOLOGY & THERAPEUTICS KING GEORGE’S MEDICAL UNIVERSITY LUCKNOW, UP

2. DEFINITION American Heart Association complex clinical syndrome that results from any structural or functional impairment of ventricular filling or ejection of blood leading to cardinal manifestations of dyspnea, fatigue, and fluid retention

3. TYPES Acute heart failure Chronic heart failure Heart Failure with Reduced Ejection Fraction( HFrEF ) Heart Failure with Preserved Ejection Fraction( HFpEF ) High-Output Heart Failure Systolic Heart Failure Diastolic Heart Failure Left Heart Failure Right Heart Failure

4. PATHOPHYSIOLOGY PROGRESSIVE DISEASE Ventricular Remodeling MECHANISMS OF DISEASE PROGRESSION Neurohormonal Activation Vasodilatory Hormones Endothelin, Inflammatory Cytokines, and Oxidative Stress Novel Biologic Targets Dyssynchrony and Electrical Instability Secondary Mitral Regurgitation

5. CARDIORENAL AND ABDOMINAL INTERACTIONS GUT CONGESTION, THE MICROBIOME, AND INFLAMMATION HIGH-OUTPUT STATES

6. SYMPTOMS Symptoms of Congestion: Pulmonary Versus Systemic Symptoms of Reduced Perfusion Other Symptoms

7. New York Heart Association Functional Classification

8. A ssessment of patients presenting with heart failure

9. PHARMACOTHERAPY Symptoms INOTROPIC DRUGS DIURETICS RAAS INHIBITORS VASODILATORS SYNTHETIC BNP BETA BLOCKERS Disease progression ACE INHIBITORS ARB’S ALDOSTERONE ANTAGONIST NEPRILYSIN INHIBITOR

10. TREATMENT PRINCIPLES Neurohumoral Modulation Preload Reduction Afterload Reduction Increasing Cardiac Contractility Heart Rate Reduction

11. Neurohumoral Modulation ACEIs ARBs β blockers MRAs

12. ANGIOTENSIN CONVERTING ENZYME INHIBITORS Mechanism of Action : Angiotensin II interacts with AT1 and AT2 4 major cardiovascular actions mediated by the AT1 receptor: vasoconstriction stimulation of aldosterone release from the adrenal glands direct hypertrophic and proliferative effects on cardiomyocytes and fibroblasts, respectively stimulation of NE release from sympathetic nerve endings and the adrenal medulla

13. Other Actions : ACE inactivates bradykinin and substance P ACEIs increase bradykinin and substance P levels 2 prominent consequences: cough , the most frequent ADR (~5%); and angioedema , a rare (~0.7%), but life-threatening condition presenting with swelling of the skin and mucous membranes of the throat and asphyxia

14. Examples of ACE Inhibitors: Captopril Enalapril Lisinopril Ramipril Trandolapril

15. Adverse effects of ACE Inhibitors Dry cough Creatinine plasma concentration increase Hypotension Hyperkalemia Angioedema Allergic skin reactions Contraindication: Bilateral renal artery stenosis

16. ANGIOTENSIN RECEPTOR ANTAGONISTS highly selective competitive antagonists at the AT1 receptors AT1 receptor mediates major effects of Angiotensin II therapeutic alternatives to ACEIs and second choice in all stages of heart failure in patients who do not tolerate ACEIs same pharmacological profile as ACEIs with the exception of not inducing cough

17. Examples of ARB’s: Candesartan Losartan Valsartan Adverse effects: Similar to ACE but no cough Contraindications : As ACEI

18. Β ETA ADRENERGIC RECEPTOR ANTAGONISTS Major Effects of catecholamines on heart(beta 1) : Increase heart rate ( chronotropy ) Increase force of contraction ( inotropy ) Quicken the rate of force development ( clinotropy ) Accelerate cardiac muscle relaxation ( lusitropy ) Acceleration of the atrial-ventricular conduction rate ( dromotropy ) Enhance cardiac myocyte automaticity Lower the threshold for arrhythmias ( bathmotropy )

19. β blockers competitively: reduce heart rate and force slow relaxation slow AV conduction suppress arrhythmia lower renin levels

20. therapy must be initiated in a clinically stable condition and at very low doses (1/8 of target ) dose escalation requires time (e.g., doubling every 4 weeks in ambulatory settings) “ start low, go slow ”

21. Available Agents: Metoprolol - β1 -selective agents B isoprolol - β1 -selective agents Nebivolol - β1 selective additional vasodilatory actions Carvedilol - nonselective β blocker and α1 receptor antagonist

22. Clinical Use: All patients with symptomatic heart failure and all patients with left ventricular dysfunction after myocardial infarction should be treated with a β blocker S hould not be administered in new-onset or acutely decompensated heart failure Precautions: Heart rate lowering( 60-70 desirable) AV block (consider pacemaker) Bronchoconstriction (C/I in allergic bronchial asthma) Peripheral vasoconstriction (cold extremities)

23. MINERALOCORTICOID RECEPTOR ANTAGONISTS Mechanism of Action : MRAs act as antagonists of nuclear receptors of aldosterone are K+-sparing diuretics additional efficacy in suppressing the consequences of neurohumoral activation Examples: spironolactone Eplerenone ( FDA approved) Adverse effect: Hyperkalemia

24. Guidelines for the use of MRAs in patients with heart failure are: Administer no more than 50 mg/day Do not use if the GFR is less than 30 mL/min (creatinine ~ 2 mg/ dL ) Be careful with elderly patients Be careful with diabetics, who carry a higher risk of hyperkalemia Do not combine with other K+-sparing diuretics

25. ANGIOTENSIN RECEPTOR AND NEPRILYSIN INHIBITOR( ARNI) Sacubitril /Valsartan made by cocrystallizing valsartan with sacubritril prodrug that inhibits neprilysin peptidase - mediates enzymatic degradation and inactivation of natriuretic peptides, bradykinin , and substance P inhibition of the RAAS natriuresis , diuresis and vasodilation inhibit thrombosis, fibrosis, cardiac myocyte hypertrophy, and renin release

26. PRELOAD REDUCTION Loop Diuretics MOA: inhibit the Na+-K+-2Cl symporter in the ascending limb of the loop of Henle Examples: furosemide torasemide Bumetanide Adverse effects: hypokalemia , hyponatremia, hypomagnesemia, hyperuricemia, hypocalcemia , glucose intolerance

27. Thiazide Diuretics MOA: Blocks Na +-Cl cotransporter in the distal convoluted tubule Examples: hydrochlorothiazide, chlorthalidone Adverse effects: Hypokalemia , hyponatremia, hypomagnesemia, hyperuricemia, hypercalcemia, glucose intolerance

28. K+-Sparing Diuretics MOA: inhibit apical Na+ channels in distal segments of the tubule directly ( ENaC ; e.g., amiloride , triamterene) or reduce its gene expression (MRAs spironolactone and eplerenone ) weak diuretics Adverse effects: Hyperkalemia , gynecomastia, erectile dysfunction and menstrual bleeding disorders (spironolactone)

29. AFTERLOAD REDUCTION F ailing heart is exquisitely sensitive to increased arterial resistance Vasodilators are beneficial in heart failure by reducing afterload and allowing the heart to expel blood against lower resistance

30. Hydralazine–Isosorbide Dinitrate fixed-combination formulation in use contains 37.5 mg hydralazine and 20 mg ISDN and is uptitrated Adverse effects: Hypotension Dizziness Headache Hydralazine doses greater than 200 mg have been associated with lupus erythematosus

31. INCREASING CARDIAC CONTRACTILITY Failing heart is unable to generate force sufficient to meet the needs of the body for perfusion of oxygenated blood Unfortunately, when used chronically, these agents do not improve life expectancy or cardiac performance Chronic use is associated with excess mortality Only cardiac glycosides are used in the treatment of chronic heart failure

32. Cardiac Glycosides Digoxin Digitalis lanata Only glycoside currently in use Increases force of contraction Decreases heart rate Other use- control of ventricular rate in atrial fibrillation/flutter

33. Mechanism of action of Digoxin

34. Adverse Effects : Therapeutic index extremely narrow 0.5 and 0.8 ng/ml - beneficial effects 1.2 ng/ml and greater- increased mortality Arrythmias - most frequent and dangerous GI symptoms- anorexia, nausea and vomiting Visual effects-altered color perception and coronas (halos) Antidote : Antidigoxin immunotherapy Purified fab fragments from ovine antidigoxin antisera ( digibind )

35. HEART RATE REDUCTION Ivabradine selective inhibitor of cardiac pacemaker channels / funny currents given to patients with sinus rhythm with hr > 70 bpm with with systolic dysfunction (EF<35%)

36. Drug Treatment of Acutely Decompensated Heart Failure Diuretics Vasodilators- N itroglycerin , Nitroprusside and N eseritide Positive Inotropic Agents- Dobutamine , Epinephrine, Nor-epinephrine, Dopamine Phosphodiesterase Inhibitors- Milrinone and Enoximone Myofilament Calcium Sensitizers- Levosimendan and Pimobendan Other Drugs- T olvaptan , Heparin and other anticoagulants