1. Pharmacological Therapy of Heart Failure: Case presentations Steven W. Harris MHS, PA-C

3. Heart Failure Complex diagnosis that results from structural or functional disorder(s) which impair the ability of the ventricle to fill with or eject blood. – ACC 2005 Complex diagnosis that results from structural or functional disorder(s) which impair the ability of the ventricle to fill with or eject blood. – ACC 2005

4. Epidemiology Prevalence Prevalence Affects 5+ million Americans currently, >600,000 new cases diagnosed each year. 23 million people worldwide. Affects 5+ million Americans currently, >600,000 new cases diagnosed each year. 23 million people worldwide. Estimates are based only on symptomatic HF. Estimates are based only on symptomatic HF. Cost Cost Annual direct cost is >10 billion dollars Annual direct cost is >10 billion dollars Frequency Frequency It is the most common inpatient diagnosis in the US for patients over 65 years of age It is the most common inpatient diagnosis in the US for patients over 65 years of age In 2004, there were over one million hospitalizations in the US with a first listed discharge diagnosis of HF In 2004, there were over one million hospitalizations in the US with a first listed discharge diagnosis of HF

5. Major Determinants of Cardiac Function Ventricular systolic function Ventricular systolic function Ventricular diastolic function Ventricular diastolic function Ventricular preload Ventricular preload Ventricular afterload Ventricular afterload Cardiac rate and conduction Cardiac rate and conduction Myocardial blood flow Myocardial blood flow

6. Ventricular Systolic Function Systolic dysfunction accounts for 60- 70% of all cases of HF Systolic dysfunction accounts for 60- 70% of all cases of HF Ejection fraction decreased Ejection fraction decreased 55-65% normal 55-65% normal 40-50% mild 40-50% mild 30-40% moderate 30-40% moderate <30% severe systolic dysfunction <30% severe systolic dysfunction

7. NYHA Classification Class I - symptoms only at activity levels that would limit normal individuals Class I - symptoms only at activity levels that would limit normal individuals Class II – symptoms with ordinary exertion (moderate exertion) Class II – symptoms with ordinary exertion (moderate exertion) Class III - symptoms with less than ordinary exertion (minimal exertion) Class III - symptoms with less than ordinary exertion (minimal exertion) Class IV - symptoms at rest Class IV - symptoms at rest

8. Heart Failure Stages Stage A — High risk for HF, without structural heart disease or symptoms Stage A — High risk for HF, without structural heart disease or symptoms Stage B — Heart disease with asymptomatic left ventricular dysfunction Stage B — Heart disease with asymptomatic left ventricular dysfunction Stage C — Prior or current symptoms of HF Stage C — Prior or current symptoms of HF Stage D — Advanced heart disease and severely symptomatic or refractory HF Stage D — Advanced heart disease and severely symptomatic or refractory HF

9. Classification of HF severity 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 IAsymptomatic IISymptomatic with moderate exertion IVSymptomatic at rest IIISymptomatic with minimal exertion None

10. Treatment Objectives Decrease Symptoms Improve tissue perfusion Increase exercise tolerance Quality of/Prolong Life /Survival Correct aggravating/precipitating factors: Arrhythmias Pregnancy Infections Hyperthyroidism Thromboembolism Endocarditis Endocarditis Obesity Hypertension Physical activity Dietary excess Medications  Preload  Afterload  Ionotropy Optimize chonotropy  Neurohormonal activity

12. Vicious Cycle Chronic HF SOB, Wt gain Providers office PO Lasix ER IV Lasix +/-admit Home

13. Case 1 76 y/o moderately obese male with a history of CAD with associated CABG x 4, presents to your clinic c/o dyspnea on exertion, 2 pillow orthopnea, bilateral lower extremity edema. 76 y/o moderately obese male with a history of CAD with associated CABG x 4, presents to your clinic c/o dyspnea on exertion, 2 pillow orthopnea, bilateral lower extremity edema.

14. Case 1 Meds: Meds: Simvastatin 80mg po qhs Simvastatin 80mg po qhs Synthroid 125 mcg po qd Synthroid 125 mcg po qd Lisinopril 5 mg po qd Lisinopril 5 mg po qd Metoprolol 50 mg po qd Metoprolol 50 mg po qd ASA 81 mg 2 tabs po qd ASA 81 mg 2 tabs po qd PMH PMH ?? ?? Physical exam: Vitals BP: 146/78 HR: 78 regular RR: 12 bpm T: 98.6 F SPO2: 95% on RA JVD at 5 cm above sternal angle Bilateral rales to mid lung fields 1+ bilat pedal edema

15. Case 1 Plan: Plan: Diagnostics: Diagnostics: Treatment: Treatment: Patient Education: Patient Education: Follow-up/ Referrals: Follow-up/ Referrals: Echocardiogram BMP BNP Lasix 20 mg po qd KCL 10 meq po qd f/u in 1 wk

17. Case 2 65 y/o female who is 6 months s/p AWMI c/o 10 lb weight gain over 72 hours. Associtated sx include orthopnea, pnd, dyspnea at rest and abdominal “fullness”. At the time of discharge 6 months prior she had an ischemic cardiomyopathy with an EF of 50% 65 y/o female who is 6 months s/p AWMI c/o 10 lb weight gain over 72 hours. Associtated sx include orthopnea, pnd, dyspnea at rest and abdominal “fullness”. At the time of discharge 6 months prior she had an ischemic cardiomyopathy with an EF of 50%

18. Case 2 Meds: Meds: Quit meds Quit meds ASA 81 mg 1 tab po qd ASA 81 mg 1 tab po qd PMH PMH DM DM HTN HTN Dyslipidemia Dyslipidemia Physical exam: Vitals BP: 130/78 HR: 100 regular RR: 18 bpm T: 98.7 F SPO2: 90% on RA JVD at 10 cm above sternal angle Hepato-Jugular reflux to angle of mandible Bilateral rales 2/3 up 1+ bilat pedal edema

19. Case 2 Plan: Plan: Diagnostics: Diagnostics: Treatment: Treatment: Patient Education: Patient Education: Follow-up/ Referrals: Follow-up/ Referrals: Admit to hospital Echocardiogram CMP, BNP, CBC… Lasix 40 mg IV x 1 Then 40 mg po BID Enalapril 2.5 mg BID Simvastatin 20 mg qhs Morning labs

23. Case 2 Morning Results: Morning Results: Diuresed 3 liters Diuresed 3 liters Feeling much better Feeling much better EF 45% EF 45% BNP 550 BNP 550 Vitals: Vitals: BP 122/76 BP 122/76 HR 78 HR 78 RR 12 RR 12 T 98.6 T 98.6 SPO2 98 % on 2 L SPO2 98 % on 2 L Plan Plan Plan: Wean O2 Carvedilol 3.125 mg BID Continue Furosemide dose Morning labs

24. Beta blockers

25. Case 3 65 y/o male with known history of prior MI and CABG, ischemic cardiomyopathy with an EF of 30% presents to the ER with dyspnea at rest. He states that over the last week he has gained “at least 10 lbs” and has been sleeping in his armchair. 65 y/o male with known history of prior MI and CABG, ischemic cardiomyopathy with an EF of 30% presents to the ER with dyspnea at rest. He states that over the last week he has gained “at least 10 lbs” and has been sleeping in his armchair.

26. Case 3 Meds: Meds: Carveidolol 12.5 mg BID Carveidolol 12.5 mg BID Lisinopril 5 mg qd Lisinopril 5 mg qd Atorvastatin 40 mg qhs Atorvastatin 40 mg qhs Furosemide 80 mg qAM Furosemide 80 mg qAM ASA 81 mg 1 tab po qd ASA 81 mg 1 tab po qd PMH PMH HTN, Dyslipidemia HTN, Dyslipidemia ?? ?? Physical exam: Vitals BP: 110/78 HR: 110 regular RR: 22 bpm T: 98.7 F SPO2: 88% on RA Sitting upright JVD above angle of the mandible Hepato-Jugular reflux to angle of mandible Diffuse bilateral rales 2+ bilat pedal edema

27. Case 3 Plan: Plan: Diagnostics: Diagnostics: Treatment: Treatment: Patient Education: Patient Education: Follow-up/ Referrals: Follow-up/ Referrals: Admit to hospital Echocardiogram CMP, BNP, CBC… Bumetanide 1 mg IV then 0.5 gtt KCL repletion 2 gm sodium diet

29. Case 3 Results Results Diuresed 4 liters Diuresed 4 liters Weaned from IV to PO Furosemide Weaned from IV to PO Furosemide 80 mg po qd 80 mg po qd Cr 1.5 Cr 1.5 Slowly gaining H2O weight Slowly gaining H2O weight What can you do? What can you do? Sequential nephron blockade. Sequential nephron blockade. Addition of aldosterone antagonist Addition of aldosterone antagonist Sequential nephron blockade with: Metolazone 2.5 mg po qd Aldosterone antagonist Spironolactone 25 mg daily f/u labs K+ in 3 days and one week. Increased Risk of hyperkalemia if Cr >1.6

31. Case 3 Consideration of positive inotropes Consideration of positive inotropes Dobutamine 2-20 mcg/kg/min IV Dobutamine 2-20 mcg/kg/min IV Indications: insufficient cardiac output Indications: insufficient cardiac output Effect: Increase Cardiac output and stroke volume Effect: Increase Cardiac output and stroke volume Comment: Tachycardia, hypertension, hypotension Comment: Tachycardia, hypertension, hypotension Dopamine. 2-20 mcg/kg/min IV Dopamine. 2-20 mcg/kg/min IV Indications: Insufficient cardiac output, hypotension, reduced renal perfusion Indications: Insufficient cardiac output, hypotension, reduced renal perfusion Effect: Increase cardiac output, stroke volume, and renal blood flow Effect: Increase cardiac output, stroke volume, and renal blood flow Digoxin Digoxin

32. Digoxin Mildly positive inotropic effects Mildly positive inotropic effects Associated with symptomatic improvement, increase exercise tolerance, and clinical stability Associated with symptomatic improvement, increase exercise tolerance, and clinical stability Pts taking digoxin are less likely to be hospitalized (25% reduction) due to CHF. Pts taking digoxin are less likely to be hospitalized (25% reduction) due to CHF. Additive benefits to Diuretic, ACE, Beta blocker therapy Additive benefits to Diuretic, ACE, Beta blocker therapy

33. Case 4 60 y/o male with known history of CAD and prior MI presents to your clinic to establish care. He states that over the last month he has had to double his water pill to keep his legs thin and breathe well at night. His most recent EF was 50% one year ago. Currently he is feeling fine, but has SOB with riding his road bike. 60 y/o male with known history of CAD and prior MI presents to your clinic to establish care. He states that over the last month he has had to double his water pill to keep his legs thin and breathe well at night. His most recent EF was 50% one year ago. Currently he is feeling fine, but has SOB with riding his road bike.

34. Case 4 Meds: Meds: Enalapril 20 mg qd Enalapril 20 mg qd Cardizem CD 180 mg qd Cardizem CD 180 mg qd Atorvastatin 40 mg qhs Atorvastatin 40 mg qhs HCTZ 25 mg 2 tabs po qd HCTZ 25 mg 2 tabs po qd ASA 81 mg 1 tab po qd ASA 81 mg 1 tab po qd Naproxen 220 mg qd Naproxen 220 mg qd PMH PMH HTN, Dyslipidemia HTN, Dyslipidemia ?? ?? Physical exam: Vitals BP: 118/78 HR: 64 regular RR: 12 bpm T: 98.7 F SPO2: 97% on RA JVD 3 cm above sternal angle Clear lung fields Trace bilateral pedal edema

35. Case 4 Plan: Plan: Diagnostics: Diagnostics: Treatment: Treatment: Patient Education: Patient Education: Follow-up/ Referrals: Follow-up/ Referrals: DC Cardizem Start: Carvedilol 6.25 mg BID and uptitrate to 12.5 mg BID in two weeks DC Naproxen Consider acetaminophen BMP to eval K+ Echocardiogram F/u 2 weeks

36. Case 5 80 y/o female c/o of 1 week h/o palpitations and 3 days of SOB and orthopnea 80 y/o female c/o of 1 week h/o palpitations and 3 days of SOB and orthopnea

37. Considerations African Americans African Americans CRF CRF ACE intolerant ACE intolerant