1. Heart Failure By: Hala M. Al-Khalidi, Pharm.D. Faculty of Pharmacy Clinical Pharmacy Division KAAU

2. Epidemiology HF is most commonly diagnosed at ages > 65 yo, more frequent in men then women. Approximately 400,000 new cases each year. A 4 fold increase in hospitalization over the past 20 years. The five-year survival rate is about 30-40% for HF patients. Class IV heart failure patients, the 1 year survival rate is only 50%.

3. Definition Heart failure (HF) is defined as a syndrome in which the heart fails to pump sufficient blood to meet the needs of the body Ejection fraction (EF) = % of the end-diastolic volume that is ejected during systole (normal > 50%) Preload - is the volume of blood that fills the ventricle during diastole (filling of blood) creating tension or stretch on the ventricle Contractility - is the force with which left ventricular ejection occurs, it's independent of preload & afterload effects Afterload - is the ventricular tension that occurs during systole (contraction & ejection of blood)

4. Etiology Systolic Dysfunction ↓EF + ↑LVEDV ↓EF + ↑LVEDV - Ischemic disease Myocardial Ischemia, & MI. - Non- Ischemic disease ◘1 ry Myocardial muscle dysfunction(idiopathic, alc.,drug- iduced, familial). ◘1 ry Myocardial muscle dysfunction(idiopathic, alc.,drug- iduced, familial). ◘ Valvular abnormalities. ◘ Valvular abnormalities. ◘ Structural damage +/- damage to myocardial walls (e.g. ventricualr septal defects). ◘ Structural damage +/- damage to myocardial walls (e.g. ventricualr septal defects). ◘ Hypertension (plumonary, systemic). ◘ Hypertension (plumonary, systemic). Dilated Cardiomyopathy

5. Etiology Diastolic Dysfunction Diastolic Dysfunction ↔↓EF + ↑LVEDV ↔↓EF + ↑LVEDV ◘Hypertension ◘Amyloidosis ◘ Hypertension ◘ Amyloidosis ◘Myocardial Ischemia ◘Sarcoidosis ◘ Myocardial Ischemia ◘ Sarcoidosis Hypertrophy CardiomyopathyRestrictiveCardiomyopathy

6. Pathophysiology Systolic Dysfunction I mpaired ventricular contraction I mpaired ventricular contraction Target therapy of systolic dysfunction Target therapy of systolic dysfunction EF < 40% EF < 40% Diastolic Dysfunction I mpaired relaxation/filling of ventricle I mpaired relaxation/filling of ventricle ( often occurs along with systolic dysfunction) ( often occurs along with systolic dysfunction) Target therapy Target therapy EF ≥ 45% EF ≥ 45%

7. Right-sided vs Left-sided HF Right-sided Abd. pain, anorexia, nausea, constipation Peripheral Edema, JVD, hepatojugular reflex. Left-sided Dyspnea on exertion, Dyspnea on exertion, PND, orthopnea, Cough PND, orthopnea, Cough Pulmonary edema, Bibasilar rales Pulmonary edema, Bibasilar rales Pleural effusion, (+) S3 Gallop. Pleural effusion, (+) S3 Gallop. Non-specific Symptoms Fatigue, weakness Fatigue, weakness Cardiomegaly, Pallor. Cardiomegaly, Pallor.

8. HF Classification System New York Heart Association Functional Classification: - Class I No Limitation of physical activity. - Class I No Limitation of physical activity. - Class II ordinary activity results in symptoms - Class II ordinary activity results in symptoms of HF. of HF. - Class III Marked limitation of physical activity. - Class III Marked limitation of physical activity. - Class IV Symptoms of HF at rest. - Class IV Symptoms of HF at rest.

9. Other Precipitating Causes Infection : Fever, tachycardia, hypoxemia, and increased metabolic demand place further strain on heart. Anemia: lack of oxygenating RBC demands heart to increase output-failing heart unable to do so. Pregnancy: For tissue to be adequately perfused, increased output is needed. Arrythmias: Erratic cardiac output. Physical, dietary, fluid, environmental and emotional excesses: Any may precipitate heart failure that was previously compensated.

10. Drugs that may exacerbate HF & Other precipitating causes Negative inotropic effect - Anti-arrythmics, CCB (non-DHP). - Anti-arrythmics, CCB (non-DHP).Cardiotoxic - Doxorubicin, daunomycin, cyclophosphamide. - Doxorubicin, daunomycin, cyclophosphamide. Na + /H 2 O retention - Glucocorticoids, androgens, estrogens, NSAIDs, salicylates(high dose), Na + containing drugs. - Glucocorticoids, androgens, estrogens, NSAIDs, salicylates(high dose), Na + containing drugs.

11. Morbidity & Mortality Number of death due to CHF (1 ry & 2 ry ) increased 6- fold during the past 40 years 5 year survival is 30-40% once diagnosed 1 year survival is 50% for patients in class IV 3.5 million hospitalization, a 4-fold increase over last 2 decades Twice the costs of all forms cancer, up to 50 billion annually Leading cause of hospitalization in pts. > 65 yo

13. Evaluation of HF A. Assign stage of HF based on evaluation & progression of clinical findings (ACC/AHA Guidelines for the Evaluation & Management of Chronic Heart Failure) B. Obtain LVEF via 2-dimensional echocardiogram (EF%, systolic, diastolic, & valvular disease) (EF%, systolic, diastolic, & valvular disease) C. Ventricular hypertrophy & chest congestion can be provided by chest X-ray (cardiomegaly, plural effusion) D. ECG D. ECG E. liver enzyme elevation (heptomegaly) F. Assess fluid status: weight Peripheral edema weight Peripheral edema JVD Hepato/splenomegaly JVD Hepato/splenomegaly Rales Rales

14. Management of HF Goals of treatment: - Improve symptoms, QOL, and prolong life. - Prevention and progression to sever HF & cardiogenic shock. Non-pharmacologic/ Adjunct therapy Non-pharmacologic/ Adjunct therapy 1. Minimize sodium intake (<3gmdaily). 1. Minimize sodium intake (<3gmdaily). 2. Weight loss. 3. Smoking cessation. 2. Weight loss. 3. Smoking cessation. 4. EtOH limitation. 5. A form of exercise. 4. EtOH limitation. 5. A form of exercise. 6. surgical; correction of valvular disease, revascularization, heart transplant. 6. surgical; correction of valvular disease, revascularization, heart transplant. 7. Avoide NSAID’s. 8. Flu/Pneumococcoal vac. 7. Avoide NSAID’s. 8. Flu/Pneumococcoal vac.

15. Management of HF Pharmacological treatment Most patients with symptomatic LVD should be managed with combination of 4 types of drugs: Most patients with symptomatic LVD should be managed with combination of 4 types of drugs: - ACEI,& B-B (improve EF effecting remodling), Diuretics, +/- Digitals, form the basic core for tx. HF, - ACEI,& B-B (improve EF effecting remodling), Diuretics, +/- Digitals, form the basic core for tx. HF, hydralazine, & isosorbide for pt. who can’t take ACEI. hydralazine, & isosorbide for pt. who can’t take ACEI. - Oxygination, and hospitalization. - Oxygination, and hospitalization. - These drugs were established in large-scale clinical trials. - These drugs were established in large-scale clinical trials. {Evaluation and management of chronic heart failure in the adult feb.2002.} {Evaluation and management of chronic heart failure in the adult feb.2002.}

16. Dosing of treatment cont. vasodilatorsHydralazine Isosorbide dinitrate 10mg tid 75mg tid-qid 40mg tid 100mg 120mg Spironolactone 25mg qd 25-50mg qd 100mg

17. Management HF Anticoagulation is not recommended, only in HF patients at risk with; - AF, DVT, & PE - EF ≤ 25% may give warfarin Antiarrhythmic therapy only AF, VT, is the mode of death in up to 50% of HF cases, class I antiarrthymic not recommended, amiodarone 1 st line agent (NSR-AF) & dofetilide appear to be safe, does not appear to increase mortality.

18. Clinical studie’s endpoints Significant reduction in HF Progression improve (S&S). Significant reduction in hospitalization. Improve exercise capacity. Significant reduction in morbidity & mortality.

19. Important Thing To Do Take your scheduled medications, missing doses may worsen condition. A system reminder pill box, calender. Refill med’s before running out. Discuss medications S.E. with your doctor. Discuss if less expensive medications would work.o Carry an updated list of medications, with each clinic visit, & include OTC’s. Weigh your self daily & record, if the weight cahnges by 3 pounds in a day, or 5pounds in a week, call your doctor..