2. Heart Failure: medication

3. Types of Heart Failure Systolic (or squeezing) heart failure –Decreased pumping function of the heart, which results in fluid back up in the lungs and heart failure Diastolic (or relaxation) heart failure –Involves a thickened and stiff heart muscle –As a result, the heart does not fill with blood properly –This results in fluid backup in the lungs and heart failure

4. Classification of HF: Comparison Between ACC/AHA HF Stage and NYHA Functional Class 1 Hunt SA et al. J Am Coll Cardiol. 2001;38:2101–2113. 2 New York Heart Association/Little Brown and Company, 1964. Adapted from: Farrell MH et al. JAMA. 2002;287:890–897. ACC/AHA HF Stage 1 NYHA Functional Class 2 AAt high risk for heart failure but without structural heart disease or symptoms of heart failure (eg, patients with hypertension or coronary artery disease) BStructural heart disease but without symptoms of heart failure CStructural heart disease with prior or current symptoms of heart failure DRefractory heart failure requiring specialized interventions I Asymptomatic II Symptomatic with moderate exertion IV Symptomatic at rest III Symptomatic with minimal exertion None

5. Compensatory Mechanisms: Renin-Angiotensin-Aldosterone System Renin + Angiotensinogen Angiotensin I Angiotensin II Peripheral Vasoconstriction  Afterload  Cardiac Output Heart Failure  Cardiac Workload  Preload  Plasma Volume Salt & Water Retention Edema Aldosterone Secretion ACE Kaliuresis BetaStimulation CO CO Na + Na + Fibrosis

6. Drug Therapy

7. Heart Failure Treatments: Medication Types ACE inhibitor (angiotensin-converting enzyme) ARB (angiotensin receptor blockers) Beta-blocker Digoxin Diuretic Aldosterone blockade Type What it does Expands blood vessels which lowers blood pressure, neurohormonal blockade Similar to ACE inhibitor—lowers blood pressure Reduces the action of stress hormones and slows the heart rate Slows the heart rate and improves the heart’s pumping function (EF) Filters sodium and excess fluid from the blood to reduce the heart’s workload Blocks neurohormal activation and controls volume

8. Rational for Medications (Why does my doctor have me on so many pills??) Improve Symptoms –Diuretics (water pills) –digoxin Improve Survival –Betablockers –ACE-inhibitors –Aldosterone blockers –Angiotensin receptor blockers (ARB’s)

9. Lifestyle Changes Eat a low-sodium, low-fat diet Lose weight Stay physically active Quit Smoking What Why Sodium is bad for high blood pressure, causes fluid retention Extra weight can put a strain on the heart Exercise can help reduce stress and blood pressure Smoking can damage blood vessels and make the heart beat faster

10. 1. АСЕ inhibitors

11. ACE inhibitors ACE inhibitors reduce pre- and afterload. They are administered in lower doses alone or together with diuretics, cardiac glycoside, antiischemic agents, etc. in all stages of CHF, due to systolic dysfunction.

12. 2. Thiazides and loop diuretics They increase salt and water loss, reduce blood volume and lower excessive venous filling pressure, reduce circulating blood volume and preload. The congestive features of oedema, in the lungs and periphery, are alleviated, cardiac output is also increased.

14. 3. Cardiac glycosides (CGs)

15. Na + /K + ATP-ase Na + /Ca 2+ exchange Ca 2+ 3Na + 2K+2K+ DIGOXIN ExIn (–)(–)

16. Digoxin: Positive inotropic effect Negative chronotropic effect Negative dromotropic effect ARs: bradycardia, AV block, Extrasystoles arrhythmias, accumulation and intoxication.

17. Potassium and calcium have antagonistic action. Hypokalemia and hypercalcemia potentiate the action of CGs.

18. Digoxin (t 1/2 40 h): p.o. or i.v. CGs are effective in CHF, occuring with normal or accelerated heart rhythm, especially in cases of atrial fibrillation.

19. In cases of severe heart failure low doses of Spironolactone are added to the therapy while regularly checking creatinine and electrolyte levels. Spironolactone is a weak diuretic. It blocks aldosterone receptors in the distal renal tubules and reduces increased aldosterone levels in CHF. 4. Aldosterone antagonists

20. In low doses (25 mg/24 h) Spironolactone potentiates the effects of ACE inhibitors. It also saves K + and Mg 2+ and has anti- arrhythmic activity. Spironolactone prevents myocardial fibrosis, caused by aldosterone, and in this way increases myocardial contractility. Similar to spironolactone is another aldosterone antagonist – Eplerenone.

21. Carvedilol is a blocker of β- and α- receptors. It also has antioxidant, vasodilating and cardioprotective effects. It decreases cardiac output, peripheral vascular resistance and afterload. Carvedilol lowers mortality with 25–67%, but it is contraindicated in CHF, occuring with cor pulmonale. The treatment begins with low doses (3.125 mg/12 h). 5. Beta- and alpha-blocking agents

22. 6. Beta-blocking agents Cardioselective beta-blocker Metoprolol decrease with 31% mortality in patients with CHF, if used in combination with diuretics, ACE inhibitors and Digoxin.

23. In congestive left-ventricular Isosorbide dinitrate heart failure Isosorbide dinitrate and Isosorbide-5-mononitrate and Isosorbide-5-mononitrate are prescribed. To prevent tolerance development are necessary 8–12 hours intervals without nitrates.

24. “The heart never stops. When it stops, it stops forever”. Leonardo da Vinci M o d e r n m e d i c i n e o f t e n d i s p r o v e s t h i s s a y i n g.