CONTEMPORARY STANDARDS IN TREATMENT OF CHRONIC HEART FAILURE

1. CONTEMPORARY STANDARDS IN TREATMENT OF CHRONIC HEART FAILURE CONTEMPORARY STANDARDS IN TREATMENT OF CHRONIC HEART FAILURE JERZY JANKOWSKI MD DEPARTMENT OF CLINICAL PHARMACOLOGY JERZY JANKOWSKI MD DEPARTMENT OF CLINICAL PHARMACOLOGY

2. http://www.zfk.ump.edu.pl/

3. Key issues in Chronic Heart FailureChronic Heart Failure (CHF) is • Common- 2% of the population • Dangerous- high mortality • Disabling- high morbidity • Costly- 2% of health care budget • Treatable- very successful pharmocological therapy developed

4. Definition of CHF • Heart failure (HF) is the inability of the heart to maintain an output adequate to meet the metabolic demands of the body. • Definition of HF I. Symptoms and signs of heart failure (at rest or during exercise) and II. Objective evidence (preferably by echocardiography) of Cardiac dysfunction (systolicand/ordiastolic) (at rest) and (in cases where the diagnosis is in doubt) and III. Response to treatment directed towards heart failure *Criteria I and II should be fulfiled in all cases.

10. Pathophysiology of Heart FailureAutonomic and hormonal control of cardiovascular function

11. Pathophysiology of Heart Failure

12. Cardiac performance is a function of 4 factors PRELOAD AFTERLOAD CONTRACTILITY HEART RATE Pathophysiology of Cardiac Performance

13. Preload

36. Diuretics in Heart Failure Loop diuretics: furosemide, torsemide Thiazide and thiazide-like diuretics: hydrochlorothiazide chlorthalidone K+ sparing diuretics: Na+ channel inhibitors: amiloride, triamterene Aldosteron antagonists: spironolactone,eplerenone

37. Diuretics in Heart Failure

38. Loop Diuretics Furosemide, torsemide, ethacrinic acide, torsemide Secreted into the tubular fluid by proximal tubule cells

39. Loop Diuretics: Side Effects and Drug Interaction • Volume depletion, hyponatremia, hypokalemia • Hypocalcemia, hypomagnesemia, hypochloremia • Ototoxicity – especially with ethacrynic acid • Hypotension • Metabolic effects – hyperuricemia, hyperglycemia, hypercholesterolemia (↑LDL, ↓HDL, ↑TGL) • Cardiac glycosides (risk of ventricular arrhythmias) • Aminoglycoside antibiotics, cisplatin (risk of ototoxicity)

40. Loop Diuretics: Drug Interaction • NSAIDs – reduced effects • Probenecid – blocks secretion into the distal tubule and decreases the response to the LD

41. Thiazide Diuretics • Hydrochlorothiazide – the prototype for this class of drugs • Thiazide-like – chlorthalidone, indapamide and metolazone (long acting diuretics) • The same mechanism of action

42. Thiazide Diuretics – Side Effects • Electrolyte abnormalities – hypokaliemia, hyponatremia, hypercalcemia, hypomagnesemia, hypochloremia, hypovolemia • Hyperuricemia, hyperglycemia (reduced effecacy of hypoglycemic drugs • Increased plasma levels of LDL and TGL • Sexual dysfunction • Cardiac arrhythmias • Drug interactions – as loop diuretics

46. Aldosterone Antagonists

47. Aldosterone Antagonists

48. Aldosterone Antagonists

49. Aldosterone Antagonists RALES TRIAL

50. RALES TRIAL