CURRENT APPROACH TO THE TREATMENT OF CONGESTIVE HEART FAILURE

1. CURRENT APPROACH TO THE TREATMENT OF CONGESTIVE HEART FAILURE

2. Treatment of CHF in 1970 • Digitalis • Diuretics • Salt restriction

3. Modern Rx of CHF • Diuretics • Vasodilators • Beta-blockers • Inotropic agents • Digoxin • Adrenergic agents • Milrinone • Aldactone • BiV Pacing

4. Diuretics • Decrease edema • Do not improve cardiac output • Improve exercise capacity • No known beneficial molecular effects • No reversed remodeling • Do not slow progression of disease • Cause pre-renal failure • Increase mortality

5. Digitalis: Effect on Hospitalizations 67.1% 64.3% Hospitalizations (%) Digoxin Placebo N Engl J Med 1997;336:525-533

6. Digitalis: Effect on Mortality 40 35.1% 34.8% Mortality % 0 Placebo Digoxin N Engl J Med 1997;336:525-533

7. “Newer” Therapies • ACE inhibitors (class effect) • Hemodynamic and molecular effects • Beta-blockers (may not be class effect) • Long-term hemodynamic benefits • Probably achieved by molecular effects • Aldactone • Probably just molecular effects • Angiotensin receptor blockers • Similar to ACE inhibitors in most ways

8. CLINICAL ASSESSMENT OF CHF • BLOOD PRESSURE • JVP • RALES • EDEMA • SERUM CREATININE • MITRAL REGURGITATION • POSTURAL SYMPTOMS • BNP

9. WHAT TO EXPECT FROM DIURETICS • RAPID RESPONSE • DECREASED FILLING PRESSURES • EDEMA BUT the tendency is for • CARDIAC OUTPUT • CREATININE • NEUROHUMORAL ACTIVATION

10. VASODILATORS • NITRATES • VENOUS • ARTERIOLAR • ARTERIAL DILATORS • HYDRALAZINE • BALANCED VASODILATORS • NITROPRUSSIDE • ACE INHIBITORS • ANGIOTENSIN RECEPTOR BLOCKERS • OMEPATRILAT (combined ACEI and NEP)

11. WHAT TO EXPECT FROM VASODILATORS • FILLING PRESSURES • CARDIAC OUTPUT • EXERCISE TOLERANCE • NEUROHUMORAL ACTIVATION • REVERSE REMODELING • HOSPITALIZATIONS and MORTALITY

12. HOW TO USE ACE INHIBITORS • PHYSIOLOGICAL APPROACH • DOSES SHOULD BE MAXIMUM TOLERATED • IN CHF, TWICE A DAY (CAPTOPRIL 3-4 TIMES/DAY) • IDEAL BLOOD PRESSURE OFTEN <100 mmHg IF NO POSTURAL SYMPTOMS • IF CHF WORSE AND HYPOTENSIVE, DON’T REDUCE THE DOSE UNLESS CLEARLY NECESSARY • KEEP PATIENT ON IT DESPITE MINOR INCREASES IN CREATININE OR POTASSIUM

13. ATLAS (high vs low dose lisinopril) Risk of all cause mortality Risk of death or hospitalization Frequency of HF hospitalizations 8 % p=0.12 12% p=0.002 % Decrease 25% p=0.002

14. WHAT TO EXPECT OF NITRATES • VENODILATATION AT LOW DOSES • ARTERIAL DILATATION AT HIGH DOSES • CARDIAC OUTPUT • MITRAL REGURGITATION • BENEFICIAL REMODELING • IMPROVED EXERCISE TOLERANCE

15. DRUG COMBINATIONS • ACE INHIBITORS AND NITRATES • ACE INHIBITORS AND ANGIOTENSIN RECEPTOR BLOCKERS • BETA-BLOCKERS • ALDACTONE • HYDRALAZINE • INOTROPES

19. Nitrates and Hydralazine • Reduce mortality • ACE/ARB-intolerant patients • Combination with ACE Inhibitors • No adverse effect on renal function • ACE Inhibitors more effective in reducing mortality • Nitrates and Hydralazine - better hemodynamic responses

20. Beta-Adrenergic Blockade in Congestive Heart Failure • Historically contraindicated in CHF • Counter-intuitive • Early studies not definitive • Anecdotes impressive • Recent trials definitive • Still slow to be adopted

21. US CARVEDILOL TRIAL

22. LVEF Carvedilol Causes a Dose-Related Improvement in LV Ejection Fraction ** 8 *p<0.005 vs. placebo **p<0.0001 vs. placebo p<0.0001 7 * 6 * 5 4 3 2 1 0 6.25 mg 12.5 mg 25 mg bid Placebo Carvedilol Circulation 1996;94:2807-2816

23. Beta-Blockers: Patient Selection • Stable Class I-IV patients • LVEF < 35% - 40% • Ischemic or non-ischemic • On ACE inhibitor, diuretics, with or without digoxin • Heart Rate > 60 bpm, no high degree a-v block • Systolic BP > 85 - 90 mmHg • No contraindications to beta-blockade

24. Initiation of Beta-Blockers in Heart Failure • Optimize control of failure first • Start at the lowest dose • Increase the dose gradually as tolerated (No sooner than every 2 weeks) • Monitor vital signs, weight, and clinical status • Adjust concomitant medications as needed

25. Time course of effects Beta-Blockade Therapy Clinical Benefit Clinical Deterioration 0 1 - 2 3 - 4 5 - 6 11 - 12 Months Am J Cardiol 1997;79:794-798

27. Recommended Monitoring During Titration of Beta-Blocker Therapy • Symptoms • Weight • Heart rate (rhythm) • Blood pressure • Jugular venous pressure • Lung auscultation

28. Management of Adverse Effects • Control chf before initiation or up-titration • Persist if possible (symptoms usually improve) • May need to consider pacing • If hypotension symptomatic, consider reducing vasodilator or diuretic dose • Deterioration on maintenance Rx, dose reduction or stopping drug usually unnecessary

29. General Approach to Rx • Look for precipitating cause • B.P, JVP and Creatinine – central to assessment and monitoring • A quick fix probably won’t work as well as re-optimizing Rx • Follow up is usually essential

30. Blood pressure • BP ~ 90-100 well-tolerated. Some tolerate 70. • If asymptomatic, don’t decrease vasodilators. • If symptomatic and JVP low, consider reducing diuretic. • If JVP increased and BP is low, can either diurese or add nitrate). • Nitrates have greater potential benefit. • Can add ARB when ACE dose is maximum tolerated.

31. JVP Elevated If BP low, consider adding a nitrate (diuretic often but not always necessary). If blood pressure ok, increase ACE/add nitrate. Fine tune with diuretic when necessary.

32. Creatinine Increasing: • Most often, this means cardiac output is decreasing, not renal artery stenosis. • Need to increase output. Don’t decrease vasodilators unless it clearly is required. • Vasodilators often improve status, diuretics are a throwback to the ’70s and signal defeat.

33. If a patient deteriorates on vasodilators • and beta-blockers: • don’t decrease the vasodilators • the beta-blocker should probably also be • continued (perhaps after the first few • hours which are needed to stabilize the • patient). • consider tailored therapy if vasodilators • appear to be at maximum-tolerated dose.

34. Case Study • 49 year old man chf due to cardiomyopathy. • BP 135/90, pulse was 90 • Jugular venous pressure 12 cm. asa. • On lasix (40 mg b.i.d.),enalapril (5 mg qd) and digoxin (.25 mg qd).

35. One approach is to diurese aggressively until dry. If you do that, you can expect decreased edema. The patient will feel better and the response is easy to measure (decreased weight, JVP, edema) and the blood pressure will probably change little.

36. Another approach is to view this as an • opportunity to improve his therapy by: • Increasing vasodilators • ?Reduce diuretics • ?Combine vasodilators • Add beta-blocker • Add aldosterone antagonist

37. Case Study An 83 year old woman with chf presents with not feeling well. B.P. is 90/60, JVP is 12 cm ASA, Creatinine is 250. Meds include Enalapril 10 mg qd, lasix 60 mg bid, Carvedilol 12.5 mg bid

38. You could just give more diuretic. What will happen? or You could manipulate the vasodilators And possibly reduce the diuretics.

39. Case Study Same patient but the JVP is low and the BP is 80/60 mmHg. What would you do?

40. Short and Long-term Goals • Short-term goals • Improve hemodynamic status • decrease filling pressures • increase output • Improve exercise capacity • Long-term goals • Reverse remodeling/slow progression • Improve cardiac function • Maintain improved hemodynamic status