Heart Failure Clinical Pharmacotherapy Jason Cavolina Internal Medicine I Major Case
Incidence <ul><li>Increases with increasing age  </li></ul><ul><li>Doubles over each successive decade </li></ul><ul><li>>...
Prevalence <ul><li>~ 4.8 million Americans have HF  </li></ul><ul><li>Men: </li></ul><ul><ul><li>50-59: 8 per 1000 </li></...
Who is at Risk? <ul><li>CAD: relative risk 8.1  </li></ul><ul><li>Diabetes: relative risk 1.9  </li></ul><ul><li>Smokers: ...
Definitions <ul><li>Heart Failure (HF):   </li></ul><ul><ul><li>The inability of the heart to provide adequate cardiac out...
Definitions <ul><li>Heart Failure (HF): </li></ul><ul><li>Types: </li></ul><ul><ul><li>Systolic Dysfunction:  Impaired car...
Definitions <ul><li>Preload:   </li></ul><ul><ul><li>Left ventricular volume and pressure increase  -> ↑  sarcomeres stret...
Definitions <ul><li>Preload:   </li></ul><ul><ul><li>B/C  ↓ renal perfusion -> ↑ renin-AG system -> aldosterone sec -> ↑ N...
Definitions <ul><li>Afterload:   </li></ul><ul><ul><li>Sum of forces preventing active forward ejection of blood by the ve...
Symptoms <ul><li>Nocturnal dyspnea </li></ul><ul><li>Orthopnea </li></ul><ul><li>Dyspnea on exertion </li></ul><ul><li>Low...
Exacerbations <ul><li>Drug and diet non-compliance  </li></ul><ul><li>Drug induced Na and water retention:  </li></ul><ul>...
Exacerbations <ul><li>β-blockers  </li></ul><ul><ul><li>↓  conduction velocity; prolonged refractory period;  ↓  automatic...
Exacerbations <ul><li>CAD </li></ul><ul><li>HTN </li></ul><ul><li>Valve/mechanical heart disease </li></ul><ul><li>Toxic c...
Measuring Severity <ul><li>Two scales: </li></ul><ul><li>New York NYHA FC:  </li></ul><ul><ul><li>I: no symptoms or limita...
Measuring Severity <ul><li>ACC/AHA Staging of Heart Failure:  </li></ul><ul><ul><li>A: no heart failure, but pt has risk f...
Treatment of Systolic HF <ul><li>Optimize current management of underlying cardiac disease </li></ul><ul><li>HTN:  ↓ hemod...
Treatment of Systolic HF <ul><li>Valve disease:  </li></ul><ul><ul><li>Valve replacement  </li></ul></ul><ul><ul><ul><li>I...
Treatment of Systolic HF <ul><li>Pharmacotherapy Goals: </li></ul><ul><ul><li>Improve symptoms </li></ul></ul><ul><ul><li>...
Treatment of Systolic HF ACC/AHA   <ul><li>Pharmacotherapeutic Management:  </li></ul><ul><ul><li>Start ACE-I first (if no...
Treatment of Systolic HF <ul><li>Non-Pharmacologic Management:  </li></ul><ul><ul><li>Encourage simple activity for class ...
Treatment of Systolic HF <ul><li>Specific Endpoints:  </li></ul><ul><ul><li>Clear lungs </li></ul></ul><ul><ul><li>Elimina...
Treatment of Systolic HF <ul><li>Monitoring:  </li></ul><ul><ul><li>Weight (daily) </li></ul></ul><ul><ul><li>RR </li></ul...
Drug Role in Systolic HF <ul><li>Loop Diuretics: Symptomatic relief </li></ul><ul><ul><li>Ethacrynic Acid [EDECRINE] ( pts...
Drug Role in Systolic HF <ul><li>Loop Diuretics: </li></ul><ul><li>Mechanism:  </li></ul><ul><ul><li>Inhibit Na/K/Cl reabs...
Drug Role in Systolic HF <ul><li>ACE-I: </li></ul><ul><ul><li>Improve survival at all levels </li></ul></ul><ul><ul><li>Ma...
Drug Role in Systolic HF <ul><li>ACE-I: </li></ul><ul><li>Mechanism:  </li></ul><ul><ul><li>Prevents formation of angioten...
Drug Role in Systolic HF <ul><li>ARB: Controversial </li></ul><ul><li>May be as or less effective as ACE-I </li></ul><ul><...
Drug Role in Systolic HF <ul><li>ARB Dosing: </li></ul><ul><ul><li>Candesartan: 4mg PO QD, titrate up by 2X at 2 week inte...
Drug Role in Systolic HF <ul><li>Hydralazine + Nitrates: </li></ul><ul><li>Less effective than ACE-I </li></ul><ul><li>Poo...
Drug Role in Systolic HF <ul><li>Hydralazine + Nitrates: </li></ul><ul><li>Dosing: </li></ul><ul><ul><li>Hydralazine 25mg ...
Drug Role in Systolic HF <ul><li>Beta Blockers (BB): </li></ul><ul><li>Certain BB shown to improve HF:  </li></ul><ul><ul>...
Drug Role in Systolic HF <ul><li>Beta Blockers (BB): </li></ul><ul><li>Contraindications: </li></ul><ul><ul><li>Heart rate...
Drug Role in Systolic HF <ul><li>Beta Blockers (BB):  </li></ul><ul><li>Mechanism: - chronotrope and inotrope </li></ul><u...
Drug Role in Systolic HF <ul><li>Beta Blockers (BB): Dosing </li></ul><ul><li>Carvedilol: initial 3.125 mg BID for 2 weeks...
Drug Role in Systolic HF <ul><li>Digoxin: </li></ul><ul><li>Symptom control  </li></ul><ul><ul><li>Fatigue, dyspnea, and e...
Drug Role in Systolic HF <ul><li>Digoxin: </li></ul><ul><li>Mechanism:  </li></ul><ul><ul><li>Inhibits Na-K-ATPase (cells ...
Drug Role in Systolic HF <ul><li>Digoxin: Dosing </li></ul><ul><li>0.125 to 0.25 mg, based upon renal function  </li></ul>...
Drug Role in Systolic HF <ul><li>Digoxin Monitoring:  </li></ul><ul><ul><li>Wait at least 5 days in pts w/ normal renal fx...
Drug Role in Systolic HF <ul><li>Digoxin Toxicity: </li></ul><ul><li>Digibind:   </li></ul><ul><ul><li>1 mg digibind binds...
Drug Role in Systolic HF <ul><li>Aldosterone Antagonist: </li></ul><ul><li>Sipronolactone: </li></ul><ul><ul><li>MOA: comp...
Drug Role in Systolic HF <ul><li>Sipronolactone Dosing: </li></ul><ul><li>ACC/AHA guidelines:  </li></ul><ul><li>25-50 mg ...
Drug Role in Systolic HF <ul><li>Risk Factors for life threatening hyperK: </li></ul><ul><li>Increasing age </li></ul><ul>...
Drug Role in Systolic HF <ul><li>Calcium Channel Blockers (CCBs): </li></ul><ul><li>Initial studies show deleterious effec...
Drug Role in Systolic HF <ul><li>Drugs contraindicated in HF: </li></ul><ul><ul><li>NSAIDs </li></ul></ul><ul><ul><li>Thia...
Drug Role in Systolic HF <ul><li>Lifestyle Modifications: </li></ul><ul><ul><li>Cessation of smoking </li></ul></ul><ul><u...
Treatment of Diastolic HF <ul><li>Definition: </li></ul><ul><ul><li>Abnormal left ventricular filling accompanied by eleva...
Treatment of Diastolic HF <ul><li>BNP: Can be used for both diagnosis and prognosis </li></ul><ul><li>BNP  >  75 pg/mL sen...
Treatment of Diastolic HF <ul><li>ACC/AHA Task Force Guidelines: </li></ul><ul><ul><li>Control of systolic and diastolic h...
Treatment of Diastolic HF <ul><li>AntiHTN therapy:  </li></ul><ul><ul><li>Mainstay of therapy in LVH due to HTN </li></ul>...
Treatment of Diastolic HF <ul><li>BB: </li></ul><ul><ul><li>Slow HR </li></ul></ul><ul><ul><ul><li>↑  time available for b...
Case <ul><li>HPI: </li></ul><ul><ul><li>MF a 82 YO WM with CC of  ↑ SOB and LL edema w/ orthopenia x10 days.  He complains...
Case <ul><li>ROS: </li></ul><ul><li>Neck: No JVD </li></ul><ul><li>Heart: </li></ul><ul><ul><li>The rhythm is regular </li...
Case <ul><li>EKG: </li></ul><ul><ul><li>bigeminy, rbbb </li></ul></ul><ul><li>Labs: </li></ul><ul><ul><li>All WNL except: ...
Case <ul><li>Active Meds: </li></ul><ul><li>DOCUSATE SODIUM (COLACE) 100MG PO TID  </li></ul><ul><li>ENOXAPARIN NA (LOVENO...
Case <ul><li>Assessment: </li></ul><ul><ul><li>New onset CHF  </li></ul></ul><ul><ul><li>Class III/class C </li></ul></ul>...
References <ul><li>American Heart Association. Heart Disease and Stroke Statistics 2004 Update. Dallas, TX: American Heart...
References <ul><li>Hunt, SA, Baker, DW, Chin, MH, et al. ACC/AHA guidelines for the evaluation and management of chronic h...
References <ul><li>McMurray, JJ, Ostergren, J, Swedberg, K, et al. Effects of candesartan in patients with chronic heart f...
References <ul><li>Zile, MR, Brutsaert, DL. New concepts in diastolic dysfunction and diastolic heart failure: Part I: dia...
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Heart Failure

  1. 1. Heart Failure Clinical Pharmacotherapy Jason Cavolina Internal Medicine I Major Case
  2. 2. Incidence <ul><li>Increases with increasing age </li></ul><ul><li>Doubles over each successive decade </li></ul><ul><li>> 40 YO = 20% lifetime chance </li></ul>
  3. 3. Prevalence <ul><li>~ 4.8 million Americans have HF </li></ul><ul><li>Men: </li></ul><ul><ul><li>50-59: 8 per 1000 </li></ul></ul><ul><ul><li>80-89: 66 per 1000 </li></ul></ul><ul><li>Women: </li></ul><ul><ul><li>50-59: 8 per 1000 </li></ul></ul><ul><ul><li>80-89: 79 per 1000 </li></ul></ul><ul><li>African-Americans: 25 % > Caucasians </li></ul>
  4. 4. Who is at Risk? <ul><li>CAD: relative risk 8.1 </li></ul><ul><li>Diabetes: relative risk 1.9 </li></ul><ul><li>Smokers: relative risk 1.6 </li></ul><ul><li>HTN: relative risk 1.4 </li></ul><ul><li>Valvular heart disease: relative risk 1.5 </li></ul><ul><li>Obesity: relative risk 1.3 </li></ul>
  5. 5. Definitions <ul><li>Heart Failure (HF): </li></ul><ul><ul><li>The inability of the heart to provide adequate cardiac output </li></ul></ul><ul><ul><li>Any structural or functional cardiac disorder impairing the ability of the ventricle to fill with or eject blood </li></ul></ul><ul><ul><li>End-stage of a number of different cardiac diseases (CAD, HTN, Pulmonary disease, Renal failure ect..) </li></ul></ul><ul><ul><li>LVEF < 50% </li></ul></ul>
  6. 6. Definitions <ul><li>Heart Failure (HF): </li></ul><ul><li>Types: </li></ul><ul><ul><li>Systolic Dysfunction: Impaired cardiac contractility = poor pumping mechanism </li></ul></ul><ul><ul><li>Diastolic Dysfunction: ↓ compliance of heart impairs ventricular filling </li></ul></ul>
  7. 7. Definitions <ul><li>Preload: </li></ul><ul><ul><li>Left ventricular volume and pressure increase -> ↑ sarcomeres stretch and ↑ force of contraction </li></ul></ul><ul><ul><li>↑ venous load -> ↑ workload of heart -> ↑ preload </li></ul></ul><ul><ul><li>systolic fxn decrease -> fluid backup and congestion of lung and right side of heart -> ↑ preload </li></ul></ul>
  8. 8. Definitions <ul><li>Preload: </li></ul><ul><ul><li>B/C ↓ renal perfusion -> ↑ renin-AG system -> aldosterone sec -> ↑ Na & water reabsorption -> ↑ blood volume </li></ul></ul>
  9. 9. Definitions <ul><li>Afterload: </li></ul><ul><ul><li>Sum of forces preventing active forward ejection of blood by the ventricle </li></ul></ul><ul><ul><ul><li>Vasoconstriction = Ejection impedance </li></ul></ul></ul><ul><ul><ul><li>Ventricular wall tension </li></ul></ul></ul><ul><ul><ul><li>Incorrect wall geometry </li></ul></ul></ul><ul><ul><li>↑ afterload -> ↓ stroke volume </li></ul></ul>
  10. 10. Symptoms <ul><li>Nocturnal dyspnea </li></ul><ul><li>Orthopnea </li></ul><ul><li>Dyspnea on exertion </li></ul><ul><li>Lower extremity edema (poor return) </li></ul><ul><li>↓ exercise tolerance </li></ul><ul><li>Altered mental status/fatigue (encephalopathy) </li></ul><ul><li>Ascites </li></ul><ul><li>Hepatic engorgement (hepatic congestion) </li></ul><ul><li>↑ jugular venous pressure (>8mmHg) </li></ul><ul><li>S 3 heart sound (R sided failure) </li></ul><ul><li>pulmonary rales (pul congestion) </li></ul>
  11. 11. Exacerbations <ul><li>Drug and diet non-compliance </li></ul><ul><li>Drug induced Na and water retention: </li></ul><ul><ul><li>Corticosteroids (chronic use) </li></ul></ul><ul><ul><li>NSAIDs, COX2 inhibitors (directly) </li></ul></ul><ul><ul><li>CCBs (DHP): </li></ul></ul><ul><ul><ul><li>↓ conduction velocity, prolong refractory period, ↓ automaticity; (verapamil and diltiazem) </li></ul></ul></ul>
  12. 12. Exacerbations <ul><li>β-blockers </li></ul><ul><ul><li>↓ conduction velocity; prolonged refractory period; ↓ automaticity; Ca blockade (indirect) </li></ul></ul><ul><li>Antiarrhythmics </li></ul><ul><ul><li>Amiodarone (III): blocks Ca, Na, and β-receptors </li></ul></ul><ul><ul><ul><li>Worsen heart failure b/c hypotension, bradycardia </li></ul></ul></ul><ul><li>Chemotherapeutic agents </li></ul><ul><ul><li>Doxorubicin: life time dose not to exceed 450-550 mg/m2 </li></ul></ul>
  13. 13. Exacerbations <ul><li>CAD </li></ul><ul><li>HTN </li></ul><ul><li>Valve/mechanical heart disease </li></ul><ul><li>Toxic cardiomyopathy (Anthracyclines, EtOH, cocaine) </li></ul><ul><li>Pulmonary disease </li></ul><ul><li>Prolonged high cardiac output (hyperthyroidism, anemia) </li></ul><ul><li>Infection (coxsacie virus, rheumatic fever) </li></ul><ul><li>Post-partum (volume overload) </li></ul><ul><li>Immunologic (heart valve destruction) </li></ul>
  14. 14. Measuring Severity <ul><li>Two scales: </li></ul><ul><li>New York NYHA FC: </li></ul><ul><ul><li>I: no symptoms or limitation with normal physical activity </li></ul></ul><ul><ul><li>II: symptoms appear with normal physical activity and minimal limitation </li></ul></ul><ul><ul><li>III: symptoms w/ less then ordinary activity; marked activity limitation </li></ul></ul><ul><ul><li>IV: Symptoms at rest; any activity results in symptoms </li></ul></ul>
  15. 15. Measuring Severity <ul><li>ACC/AHA Staging of Heart Failure: </li></ul><ul><ul><li>A: no heart failure, but pt has risk factors </li></ul></ul><ul><ul><li>B: no heart failure, but pt has ischemic heart disease </li></ul></ul><ul><ul><li>C: Symptoms of heart failure (similar to NYHA FC I, II, and III) </li></ul></ul><ul><ul><li>D: Decompensated heart failure (similar to NYHA FC IV) </li></ul></ul>
  16. 16. Treatment of Systolic HF <ul><li>Optimize current management of underlying cardiac disease </li></ul><ul><li>HTN: ↓ hemodynamic load </li></ul><ul><ul><li>↓ preload ( ↓ congestive symptoms) </li></ul></ul><ul><ul><li>↓ afterload ( ↑ cardiac contractility) </li></ul></ul><ul><ul><li>Use ACE, BB, ARB b/c improve survival in HF </li></ul></ul><ul><li>CAD: </li></ul><ul><ul><li>Strong lipid control </li></ul></ul><ul><ul><li>Revascularization (angioplasty, CABG) </li></ul></ul><ul><ul><ul><li>Improve symptom status, exercise capacity, and prognosis </li></ul></ul></ul>
  17. 17. Treatment of Systolic HF <ul><li>Valve disease: </li></ul><ul><ul><li>Valve replacement </li></ul></ul><ul><ul><ul><li>Improves cardiac function </li></ul></ul></ul><ul><ul><ul><li>May resolve symptoms </li></ul></ul></ul><ul><li>Control alcohol intake </li></ul><ul><li>Stop cocaine abuse </li></ul><ul><li>Treat obstructive sleep apnea </li></ul><ul><li>Control nutritional deficiencies </li></ul>
  18. 18. Treatment of Systolic HF <ul><li>Pharmacotherapy Goals: </li></ul><ul><ul><li>Improve symptoms </li></ul></ul><ul><ul><li>Improve myocardial function </li></ul></ul><ul><ul><li>Slow or reverse deterioration in myocardial function </li></ul></ul><ul><ul><li>Reduce mortality </li></ul></ul>
  19. 19. Treatment of Systolic HF ACC/AHA <ul><li>Pharmacotherapeutic Management: </li></ul><ul><ul><li>Start ACE-I first (if not tolerated use ARB or nitrates and hydralazine in AA) Class II-III </li></ul></ul><ul><ul><li>Add diuretics if edema occurs </li></ul></ul><ul><ul><li>If still symptomatic add digoxin (afib, rate control) </li></ul></ul><ul><ul><li>Once stabilized add β-blockers </li></ul></ul><ul><ul><li>As disease progresses add sipronolactone (Class IV) </li></ul></ul><ul><ul><li>Add other agents (such as amiodarone) if tx of complications is needed (arrhythmias) </li></ul></ul>
  20. 20. Treatment of Systolic HF <ul><li>Non-Pharmacologic Management: </li></ul><ul><ul><li>Encourage simple activity for class I – III patients </li></ul></ul><ul><ul><li>Encourage weight loss </li></ul></ul><ul><ul><li>Na and fluid restriction </li></ul></ul><ul><ul><ul><li>< 2g Na diet </li></ul></ul></ul><ul><ul><li>Discourage alcohol </li></ul></ul>
  21. 21. Treatment of Systolic HF <ul><li>Specific Endpoints: </li></ul><ul><ul><li>Clear lungs </li></ul></ul><ul><ul><li>Elimination of pitting edema </li></ul></ul><ul><ul><li>Fluid intake = Urine output </li></ul></ul><ul><ul><li>BP 130/85 or lower </li></ul></ul><ul><ul><li>RRR </li></ul></ul>
  22. 22. Treatment of Systolic HF <ul><li>Monitoring: </li></ul><ul><ul><li>Weight (daily) </li></ul></ul><ul><ul><li>RR </li></ul></ul><ul><ul><li>Pitting edema (daily) </li></ul></ul><ul><ul><li>BP </li></ul></ul><ul><ul><li>CBC (anemia worsens CHF) </li></ul></ul><ul><ul><li>Chem 7 </li></ul></ul><ul><ul><li>Drug side effects </li></ul></ul><ul><ul><li>LFTs/LETs (if pt is fluid overloaded, indicating liver congestion) </li></ul></ul><ul><ul><li>Urine output (strict I/Os) </li></ul></ul>
  23. 23. Drug Role in Systolic HF <ul><li>Loop Diuretics: Symptomatic relief </li></ul><ul><ul><li>Ethacrynic Acid [EDECRINE] ( pts w/ sulfa allergy ) </li></ul></ul><ul><ul><li>Bumetadine [BUMEX]: 40 x potent as lasix </li></ul></ul><ul><ul><li>Furosemide [LASIX] </li></ul></ul><ul><ul><li>Torsemide [DEMADEX] </li></ul></ul><ul><li>Volume overload (periph edema) </li></ul><ul><li>Dyspnea, rales </li></ul>
  24. 24. Drug Role in Systolic HF <ul><li>Loop Diuretics: </li></ul><ul><li>Mechanism: </li></ul><ul><ul><li>Inhibit Na/K/Cl reabsorption in TAL </li></ul></ul><ul><li>Side Effects: </li></ul><ul><ul><li>Ototoxicity </li></ul></ul><ul><ul><li>↑ uric acid (gout) </li></ul></ul><ul><ul><li>↑ blood sugar and ↑ lipids (at high doses) </li></ul></ul><ul><ul><li>Acute ↓ volume </li></ul></ul><ul><ul><li>K depletion (tx w/ K supplement < 3.5 mEq/L) </li></ul></ul>
  25. 25. Drug Role in Systolic HF <ul><li>ACE-I: </li></ul><ul><ul><li>Improve survival at all levels </li></ul></ul><ul><ul><li>May be ineffective in AA </li></ul></ul><ul><ul><li>Promotes progression of left ventricular hypertrophy </li></ul></ul><ul><ul><li>Beginning therapy = low doses </li></ul></ul><ul><ul><ul><li>Enalapril (Vasotec) 2.5 mg BID </li></ul></ul></ul><ul><ul><ul><li>Captopril (Capoten) 6.25 mg TID </li></ul></ul></ul><ul><ul><li>Gradually increase: As tolerated BP, SE </li></ul></ul><ul><ul><ul><li>Enalapril 10 mg BID </li></ul></ul></ul><ul><ul><ul><li>Captopril 50 mg TID </li></ul></ul></ul><ul><ul><ul><li>Lisinopril (Zestril/Prinivil) 40 mg QD </li></ul></ul></ul>
  26. 26. Drug Role in Systolic HF <ul><li>ACE-I: </li></ul><ul><li>Mechanism: </li></ul><ul><ul><li>Prevents formation of angiotensin II a potent vasoconstrictor </li></ul></ul><ul><li>Side Effects: </li></ul><ul><ul><li>Cough (10-20%) </li></ul></ul><ul><ul><li>Rash (transient and pruritic) </li></ul></ul><ul><ul><li>Dysgeusia (sweet or metallic taste) </li></ul></ul><ul><ul><li>Angioedema </li></ul></ul><ul><ul><li>Leukopenia (in high doses) </li></ul></ul><ul><ul><li>Acute renal failure </li></ul></ul><ul><ul><li>↑ K </li></ul></ul><ul><ul><li>Hypotension </li></ul></ul><ul><li>Contraindications: </li></ul><ul><ul><li>↑ K (> 5.5 mEq/L) </li></ul></ul><ul><ul><li>Symptomatic hypotension </li></ul></ul><ul><ul><li>Bilateral renal artery stenosis </li></ul></ul><ul><ul><li>Pregnancy (C-1 st / D-2 nd & 3 rd </li></ul></ul>
  27. 27. Drug Role in Systolic HF <ul><li>ARB: Controversial </li></ul><ul><li>May be as or less effective as ACE-I </li></ul><ul><li>Not to be used in preference to ACE-I </li></ul><ul><li>Beneficial in pt w/ II-III who cannot tolerate ACE-I: </li></ul><ul><ul><li>CHARM-Alternative trial = candesartan (Atacand) </li></ul></ul><ul><ul><li>Valsartan (Diovan) FDA approved </li></ul></ul><ul><ul><ul><li>ACC/AHA class IIa (weight of evidence/opinion is in favor of usefulness/efficacy) </li></ul></ul></ul><ul><li>Combo ACE-I + ARB +/- BB: </li></ul><ul><ul><li>Val-HeFT: trial had to be stopped </li></ul></ul><ul><ul><li>VALIANT: no ↑ efficacy </li></ul></ul>
  28. 28. Drug Role in Systolic HF <ul><li>ARB Dosing: </li></ul><ul><ul><li>Candesartan: 4mg PO QD, titrate up by 2X at 2 week intervals as tolerated, Target 32 mg </li></ul></ul><ul><ul><li>Valsartan: 40mg PO BID, titrate to 80-160 mg BID as tolerated, MDD 320 mg </li></ul></ul><ul><li>Mechanism: block angiotensin II receptor </li></ul><ul><li>Side Effects: same as ACE-I but without cough </li></ul><ul><li>Contraindications: same as ACE-I </li></ul>
  29. 29. Drug Role in Systolic HF <ul><li>Hydralazine + Nitrates: </li></ul><ul><li>Less effective than ACE-I </li></ul><ul><li>Poor compliance </li></ul><ul><ul><li>Large pill burden </li></ul></ul><ul><li>Indicated in pt who cannot take ACE-I/ARB </li></ul><ul><li>Beneficial in AA: Class III-IV </li></ul><ul><ul><li>A-HeFT trial (African-American Heart Failure Trial) </li></ul></ul><ul><ul><ul><li>Terminated early b/c ↓ mortality in hydralazine arm </li></ul></ul></ul>
  30. 30. Drug Role in Systolic HF <ul><li>Hydralazine + Nitrates: </li></ul><ul><li>Dosing: </li></ul><ul><ul><li>Hydralazine 25mg TID, titrated to 100 mg TID </li></ul></ul><ul><ul><li>Isosorbide DN or MN: 40mg TID/QID or 40-120 mg QD </li></ul></ul><ul><li>Mechanism: </li></ul><ul><ul><li>Hydralazine: Direct acting arterial dilator (↓ afterload) </li></ul></ul><ul><ul><li>Nitrate: Venodilator (↓ pre-load) </li></ul></ul><ul><li>Side Effects: </li></ul><ul><ul><li>Reflex tachycardia </li></ul></ul><ul><ul><li>Significant peripheral edema </li></ul></ul><ul><ul><li>Palpations </li></ul></ul><ul><ul><li>HA </li></ul></ul><ul><ul><li>Dose related SLE (hydralazine) </li></ul></ul>
  31. 31. Drug Role in Systolic HF <ul><li>Beta Blockers (BB): </li></ul><ul><li>Certain BB shown to improve HF: </li></ul><ul><ul><li>overall and event-free survival </li></ul></ul><ul><ul><li>Class II to III </li></ul></ul><ul><ul><li>Carvedilol (Coreg), Metoprolol (Toprol XL) and Bisoprolol (Zebeta) </li></ul></ul><ul><li>For all patients with symptomatic HF, unless contraindicated </li></ul><ul><ul><li>risk of worsening symptoms due to (–) inotropic effects (↓ contractility) and AV nodal block </li></ul></ul><ul><li>AVOID BB w/ ISA </li></ul><ul><ul><li>Acebutolol (Sectral) and Pindolol (Visken) </li></ul></ul>
  32. 32. Drug Role in Systolic HF <ul><li>Beta Blockers (BB): </li></ul><ul><li>Contraindications: </li></ul><ul><ul><li>Heart rate <60 bpm </li></ul></ul><ul><ul><li>Systolic pressure <100 mmHg </li></ul></ul><ul><ul><li>Signs of peripheral hypoperfusion </li></ul></ul><ul><ul><ul><li>Diminished pulses </li></ul></ul></ul><ul><ul><ul><li>Cold, pale limbs </li></ul></ul></ul><ul><ul><ul><li>Skin atrophy </li></ul></ul></ul><ul><ul><li>PR interval >0.24 sec </li></ul></ul><ul><ul><li>Heart block </li></ul></ul><ul><ul><li>Severe COPD </li></ul></ul><ul><ul><li>Asthma </li></ul></ul><ul><ul><li>Severe PVD </li></ul></ul>
  33. 33. Drug Role in Systolic HF <ul><li>Beta Blockers (BB): </li></ul><ul><li>Mechanism: - chronotrope and inotrope </li></ul><ul><li>Side effects: </li></ul><ul><ul><li>↑ blood sugar </li></ul></ul><ul><ul><li>↑ lipids (↓HDL) </li></ul></ul><ul><ul><li>↓ thyroid fxn (propranolol, metoprolol, and nadolol) </li></ul></ul><ul><ul><li>Bronchospasm (non-selective agents) </li></ul></ul><ul><ul><ul><li>Sotalol (Betapace), Nadolol (Corgard), Propranolol (Inderal) </li></ul></ul></ul><ul><ul><li>Blunts hypoglycemic response </li></ul></ul>
  34. 34. Drug Role in Systolic HF <ul><li>Beta Blockers (BB): Dosing </li></ul><ul><li>Carvedilol: initial 3.125 mg BID for 2 weeks </li></ul><ul><ul><li>Titration: 2x dose Q2W to highest dose tolerated </li></ul></ul><ul><ul><li>Max dose < 85kg 25mg PO BID </li></ul></ul><ul><ul><li>Max dose > 85kg 50mg PO BID </li></ul></ul><ul><li>Metoprolol tartrate (Lopressor): initial 6.25 mg BID </li></ul><ul><ul><li>Titration: ↑ dose gradually over 4-6w to target of 50mg BID </li></ul></ul><ul><li>Metoprolol succinate (Toprol XL) 12.5 (III-IV) or 25 (II) mg QD </li></ul><ul><ul><li>Titration: 2x Q2W to highest dose tolerated or 200 mg QD </li></ul></ul><ul><li>Bisoprolol: initial 1.25 mg QD </li></ul><ul><ul><li>Titration: to MDD 10 mg QD </li></ul></ul>
  35. 35. Drug Role in Systolic HF <ul><li>Digoxin: </li></ul><ul><li>Symptom control </li></ul><ul><ul><li>Fatigue, dyspnea, and exercise intolerance </li></ul></ul><ul><ul><li>No benefit in overall mortality </li></ul></ul><ul><ul><li>Left ventricular systolic dysfunction </li></ul></ul><ul><ul><li>LVEF <40 percent </li></ul></ul><ul><ul><li>Class II, III, and IV symptoms </li></ul></ul><ul><ul><li>While on ACE-I, BB, and if necessary a diuretic </li></ul></ul>
  36. 36. Drug Role in Systolic HF <ul><li>Digoxin: </li></ul><ul><li>Mechanism: </li></ul><ul><ul><li>Inhibits Na-K-ATPase (cells draw Ca into cell to rebalance charge   contractility); + ionotrope; augmentation of vagal tone (  rate of conduction at AV node) </li></ul></ul><ul><li>Side Effetcs: </li></ul><ul><ul><li>N/V/D </li></ul></ul><ul><ul><li>Headache </li></ul></ul><ul><ul><li>Fatigue, depression </li></ul></ul><ul><ul><li>Yellow-green halo </li></ul></ul><ul><ul><li>Cardiac arrhythmias </li></ul></ul>
  37. 37. Drug Role in Systolic HF <ul><li>Digoxin: Dosing </li></ul><ul><li>0.125 to 0.25 mg, based upon renal function </li></ul><ul><li>Levels: should be obtained at least 6 hrs after dosing = steady state </li></ul><ul><li>Serum level: 0.8-1.5 ng/mL (0.5-0.8) </li></ul><ul><ul><li>Loading dose: NOT REQUIRED </li></ul></ul><ul><ul><li>Maintenance dose: based on CrCl and age </li></ul></ul><ul><ul><li>>65y.o. </li></ul></ul><ul><ul><ul><li>CrCl <50 ml/min: 0.125 mg QOD </li></ul></ul></ul><ul><ul><ul><li>CrCl >50 ml/min: 0.125 mg QD </li></ul></ul></ul><ul><ul><li><65y.o. </li></ul></ul><ul><ul><ul><li>CrCl <50 ml/min: 0.125 mg QD </li></ul></ul></ul><ul><ul><ul><li>CrCl >50 ml/min: 0.25 mg QD </li></ul></ul></ul>
  38. 38. Drug Role in Systolic HF <ul><li>Digoxin Monitoring: </li></ul><ul><ul><li>Wait at least 5 days in pts w/ normal renal fxn before checking level </li></ul></ul><ul><ul><li>If subtherapeutic  dose by 0.125 mg and recheck in 5 days </li></ul></ul><ul><ul><li>If pt is supratherapeutic  dose by 0.125 mg and recheck in 2-3 days </li></ul></ul><ul><li>Toxicity: </li></ul><ul><ul><li>1st as N/V </li></ul></ul><ul><ul><li>Then neurological / visual disturbance </li></ul></ul><ul><ul><li>Finally cardiac arrhythmias </li></ul></ul><ul><ul><ul><li>tx w/ Digibind </li></ul></ul></ul>
  39. 39. Drug Role in Systolic HF <ul><li>Digoxin Toxicity: </li></ul><ul><li>Digibind: </li></ul><ul><ul><li>1 mg digibind binds 0.015 mg digoxin [(serum conc dig * Vss * TBW * 1000)/ 0.015 = digibind needed (ng)] </li></ul></ul><ul><ul><li>[(dig level * body wt) / 100 = # of 40 mg vials of digibind needed] </li></ul></ul>
  40. 40. Drug Role in Systolic HF <ul><li>Aldosterone Antagonist: </li></ul><ul><li>Sipronolactone: </li></ul><ul><ul><li>MOA: competes with aldosterone for the mineralocorticoid receptor </li></ul></ul><ul><ul><li>Prolong survival </li></ul></ul><ul><ul><li>K sparing diuretic </li></ul></ul><ul><li>Why use: </li></ul><ul><ul><li>↑ serum K concentration </li></ul></ul><ul><ul><li>Prevention of the adverse effects of hyperaldosteronism on the heart </li></ul></ul><ul><ul><li>Heart contains mineralocorticoid receptors </li></ul></ul>
  41. 41. Drug Role in Systolic HF <ul><li>Sipronolactone Dosing: </li></ul><ul><li>ACC/AHA guidelines: </li></ul><ul><li>25-50 mg QD in </li></ul><ul><ul><li>class IV HF </li></ul></ul><ul><ul><li>SCr < 2.5 mg/dL </li></ul></ul><ul><ul><li>K < 5 meq/L </li></ul></ul><ul><ul><li>NOT in MILD/MODERATE </li></ul></ul>
  42. 42. Drug Role in Systolic HF <ul><li>Risk Factors for life threatening hyperK: </li></ul><ul><li>Increasing age </li></ul><ul><li>More severe HF </li></ul><ul><li>Diabetes mellitus </li></ul><ul><li>Underlying renal dysfunction </li></ul><ul><li>Volume depletion </li></ul><ul><li>Higher baseline [K] </li></ul><ul><li>Spironolactone dose 50 mg/day </li></ul><ul><li>Higher ACE-I or ARB </li></ul><ul><li>Combined use of ACE-I and ARB </li></ul><ul><li>Concomitant BB </li></ul><ul><li>K supplements or K-containing salt substitutes </li></ul><ul><li>NSAIDs </li></ul>
  43. 43. Drug Role in Systolic HF <ul><li>Calcium Channel Blockers (CCBs): </li></ul><ul><li>Initial studies show deleterious effects </li></ul><ul><li>Amlodipine (Norvasc) & Felodipine (Plendil) </li></ul><ul><ul><li>Neutral effect on mortality </li></ul></ul><ul><ul><li>No direct role in HF </li></ul></ul><ul><ul><ul><li>But may still be used for angina or HTN </li></ul></ul></ul>
  44. 44. Drug Role in Systolic HF <ul><li>Drugs contraindicated in HF: </li></ul><ul><ul><li>NSAIDs </li></ul></ul><ul><ul><li>Thiazolidinediones: fluid retention </li></ul></ul><ul><ul><ul><li>Pioglitazone (Actos) </li></ul></ul></ul><ul><ul><ul><li>Rosiglitazone (Avandia) </li></ul></ul></ul><ul><ul><li>Metformin: lethal lactic acidosis </li></ul></ul><ul><ul><li>Phosphodiesterase inhibitors </li></ul></ul><ul><ul><ul><li>Cilostazol (Pletal), Sildenafil et al. </li></ul></ul></ul><ul><ul><li>Antiarrhythmics: except amioderone </li></ul></ul><ul><ul><ul><li>B/C they are - inotropes </li></ul></ul></ul>
  45. 45. Drug Role in Systolic HF <ul><li>Lifestyle Modifications: </li></ul><ul><ul><li>Cessation of smoking </li></ul></ul><ul><ul><li>Restriction of alcohol consumption </li></ul></ul><ul><ul><li>< 2g Na/day to minimize fluid accumulation </li></ul></ul><ul><ul><li>Water restriction in hyponatremic patients </li></ul></ul><ul><ul><li>Daily weight monitoring to detect fluid accumulation </li></ul></ul><ul><ul><li>Weight reduction goal within 10% of IBW </li></ul></ul><ul><ul><li>A cardiac rehabilitation program </li></ul></ul>
  46. 46. Treatment of Diastolic HF <ul><li>Definition: </li></ul><ul><ul><li>Abnormal left ventricular filling accompanied by elevated filling pressures </li></ul></ul><ul><ul><li>LVEF >50 percent </li></ul></ul><ul><li>Causes: </li></ul><ul><ul><li>Chronic hypertension with LVH </li></ul></ul><ul><ul><li>Hypertrophic cardiomyopathy (HCM) </li></ul></ul><ul><ul><li>Aortic stenosis with a normal LVEF </li></ul></ul><ul><ul><li>Ischemic heart disease </li></ul></ul><ul><ul><li>Restrictive cardiomyopathy </li></ul></ul>
  47. 47. Treatment of Diastolic HF <ul><li>BNP: Can be used for both diagnosis and prognosis </li></ul><ul><li>BNP > 75 pg/mL sensitivity of 85% and 97% specific </li></ul><ul><li>Treatment: Empiric – clinical data is limited </li></ul>
  48. 48. Treatment of Diastolic HF <ul><li>ACC/AHA Task Force Guidelines: </li></ul><ul><ul><li>Control of systolic and diastolic hypertension </li></ul></ul><ul><ul><li>Control ventricular rate in Afib </li></ul></ul><ul><ul><li>Control of pulmonary congestion and peripheral edema with diuretics </li></ul></ul><ul><ul><li>Coronary revascularization in CHD where ischemia is has adverse effect on diastolic function </li></ul></ul><ul><li>efficacy was less well established for the administration of specific drugs </li></ul>
  49. 49. Treatment of Diastolic HF <ul><li>AntiHTN therapy: </li></ul><ul><ul><li>Mainstay of therapy in LVH due to HTN </li></ul></ul><ul><ul><li>ARBs, CCBs, and ACE-I produce significantly more regression in LV mass than BB </li></ul></ul><ul><li>Antiischemic therapy: </li></ul><ul><ul><li>BB and CCBs are preferred </li></ul></ul><ul><ul><li>Nitrates may lead to hypotension </li></ul></ul><ul><ul><li>Revascularization by percutaneous coronary intervention or CABG </li></ul></ul><ul><ul><ul><li>Drug resistance </li></ul></ul></ul>
  50. 50. Treatment of Diastolic HF <ul><li>BB: </li></ul><ul><ul><li>Slow HR </li></ul></ul><ul><ul><ul><li>↑ time available for both LV filling and coronary flow </li></ul></ul></ul><ul><ul><li>↓ Myocardial O2 demand </li></ul></ul><ul><ul><li>↓ BP -> regression of LVH </li></ul></ul><ul><li>CCBs: </li></ul><ul><ul><li>lusitropic = relaxation-enhancing </li></ul></ul><ul><li>ACE-I: </li></ul><ul><ul><li>Role uncertain </li></ul></ul><ul><li>ARBs: </li></ul><ul><ul><li>May be beneficial >LVH reduction than BB </li></ul></ul><ul><li>Aldosterone Antagonist: </li></ul><ul><ul><li>Beneficial </li></ul></ul><ul><ul><li>Inhibits fibrosis and hypertrophy </li></ul></ul><ul><li>Exercise: </li></ul><ul><ul><li>Enhances diastolic fxn </li></ul></ul>
  51. 51. Case <ul><li>HPI: </li></ul><ul><ul><li>MF a 82 YO WM with CC of ↑ SOB and LL edema w/ orthopenia x10 days. He complains of ↓ ET to 1 block. Pt denies CP, palp, and syncope. </li></ul></ul><ul><li>PMH </li></ul><ul><ul><li>+ PUD/GERD, HTN, BPH </li></ul></ul><ul><ul><li>- CHF , CAD, DM, dyslipidemia </li></ul></ul><ul><li>Vitals: 10/1/05 </li></ul><ul><ul><li>BP: 137/85, 160/90 </li></ul></ul><ul><ul><li>Pulse: 78, 44 </li></ul></ul><ul><ul><li>RR: 18 </li></ul></ul><ul><ul><li>Height: 69 in </li></ul></ul><ul><ul><li>Wt:169 lb [76.8 kg] BMI = 25 </li></ul></ul>
  52. 52. Case <ul><li>ROS: </li></ul><ul><li>Neck: No JVD </li></ul><ul><li>Heart: </li></ul><ul><ul><li>The rhythm is regular </li></ul></ul><ul><ul><li>A grade 1/6 systolic murmur is present </li></ul></ul><ul><ul><li>An S3 gallop is present </li></ul></ul><ul><li>Lungs: </li></ul><ul><ul><li>There is no chest tenderness </li></ul></ul><ul><ul><li>Breath sounds are normal </li></ul></ul><ul><ul><li>Diffuse rales are heard bilaterally </li></ul></ul><ul><li>Extremities: </li></ul><ul><ul><li>No trauma </li></ul></ul><ul><ul><li>2+ bilateral leg edema </li></ul></ul>
  53. 53. Case <ul><li>EKG: </li></ul><ul><ul><li>bigeminy, rbbb </li></ul></ul><ul><li>Labs: </li></ul><ul><ul><li>All WNL except: </li></ul></ul><ul><ul><li>K (3.5-5 mEq/l): 3.5, 3.3, 3.1 </li></ul></ul><ul><ul><li>Mg (1.2-1.9 mg/dl) 1.8, 1.6 </li></ul></ul><ul><ul><li>Albumin (3.8-5.1g/dl) 3.3, 3.1, 3.5 </li></ul></ul><ul><ul><li>Hba1c: 5.2 </li></ul></ul><ul><li>Trop I: - x2 </li></ul><ul><li>BNP: 780 </li></ul><ul><li>PSA 2.5 </li></ul><ul><li>QCr = 57ml/min = 3.4l/h </li></ul><ul><li>Corrected Ca = 10mg/dl </li></ul>
  54. 54. Case <ul><li>Active Meds: </li></ul><ul><li>DOCUSATE SODIUM (COLACE) 100MG PO TID </li></ul><ul><li>ENOXAPARIN NA (LOVENOX) INJ 80MG/0.8ML SC Q12H </li></ul><ul><li>FINASTERIDE TAB 5MG PO QD </li></ul><ul><li>FUROSEMIDE INJ,SOLN 40MG/4ML IV Q12H </li></ul><ul><li>HEMORRHOIDAL PRODUCTS SUPP,RTL 1 SUPPOSITORY(IES) RTL QHS </li></ul><ul><li>OMEprazole (prILOSEc for Inpatient use) 20MG PO QAM </li></ul><ul><li>POTASSIUM CHLORIDE 20MEQ/PACKET 40MEQ/2PKT PO QD </li></ul><ul><li>WARFARIN NA (COUMADIN) 5MG TAB 5MG PO QHS </li></ul><ul><li>clonIDINE HCL (CATAPRES) TAB 0.3MG PO TID </li></ul><ul><li>liSINOpril TAB 10MG PO QAM </li></ul>
  55. 55. Case <ul><li>Assessment: </li></ul><ul><ul><li>New onset CHF </li></ul></ul><ul><ul><li>Class III/class C </li></ul></ul><ul><li>Plan: </li></ul><ul><ul><li>Increase lisinopril as per BP </li></ul></ul><ul><ul><li>Continue clonidine 0.3mg TID </li></ul></ul><ul><ul><li>KCL 10mEq powder (maintain K >4) </li></ul></ul><ul><ul><li>Continue Lasix 40mg PO AM </li></ul></ul><ul><ul><li><2g Na Diet </li></ul></ul><ul><ul><li>Daily wt </li></ul></ul>
  56. 56. References <ul><li>American Heart Association. Heart Disease and Stroke Statistics 2004 Update. Dallas, TX: American Heart Association; 2003 </li></ul><ul><li>Ho, KK, Pinsky, JL, Kannel, WB, Levy, D. The epidemiology of heart failure: the Framingham Study. J Am Coll Cardiol 1993; 22:6A. </li></ul><ul><li>Johnson JA, Parker RB and Patterson JH. Heart failure. In Dipiro et. al. editors. Pharmacotherapy: a pathophysiologic approach 5 th ed. New York:Mcgraw Hill, 2002:60,185-218 </li></ul><ul><li>Lloyd-Jones, DM, Larson, MG, Leip, EP, et al. Lifetime risk for developing congestive heart failure: the Framingham Heart Study. Circulation 2002; 106:3068. </li></ul><ul><li>He, J, Ogden, LG, Bazzano, LA, et al. Risk factors for congestive heart failure in US men and women: NHANES I epidemiologic follow-up study. Arch Intern Med 2001; 161:996 </li></ul>
  57. 57. References <ul><li>Hunt, SA, Baker, DW, Chin, MH, et al. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: executive summary. A report of the American College of Cardiology/American Heart Association task force on practice guidelines (committee to revise the 1995 guidelines for the evaluation and management of heart failure) developed in collaboration with the International Society for Heart and Lung Transplantation endorsed by the Heart Failure Society of America. J Am Coll Cardiol 2001; 38:2101 </li></ul><ul><li>Packer, M, Poole-Wilson, PA, Armstrong, PW, et al, on behalf of the ATLAS Study Group. Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. Circulation 1999; 100:2312. </li></ul>
  58. 58. References <ul><li>McMurray, JJ, Ostergren, J, Swedberg, K, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial. Lancet 2003; 362:767. </li></ul><ul><li>Cohn, JN, Tognoni, G. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med 2001; 345:1667. </li></ul><ul><li>Pfeffer, MA, McMurray, JJ, Velazquez, EJ, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 2003; 349:1893 </li></ul><ul><li>Taylor, AL, Ziesche, S, Yancy, C, et al. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med 2004; 351:2049. </li></ul><ul><li>Eichhorn, EJ, Bristow, MR. Practical guidelines for initiation of beta-adrenergic blockade in patients with chronic heart failure. Am J Cardiol 1997; 79:794 </li></ul>
  59. 59. References <ul><li>Zile, MR, Brutsaert, DL. New concepts in diastolic dysfunction and diastolic heart failure: Part I: diagnosis, prognosis, and measurements of diastolic function. Circulation 2002; 105:1387 </li></ul><ul><li>Aurigemma, GP, Gaasch, WH. Clinical practice. Diastolic heart failure. N Engl J Med 2004; 351:1097 </li></ul><ul><li>Hunt, SA, Baker, DW, Chin, MH, et al. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: executive summary. A report of the American College of Cardiology/American Heart Association task force on practice guidelines (committee to revise the 1995 guidelines for the evaluation and management of heart failure) developed in collaboration with the International Society for Heart and Lung Transplantation endorsed by the Heart Failure Society of America. J Am Coll Cardiol 2001; 38:2101. </li></ul>
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