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 DigoxinPlacebo 67.1% 64.3% Hospitalizations (%) N Engl J Med 1997;336:525-533

6. Digitalis: Effect on Mortality Digoxin Placebo 35.1% 34.8% 0 40 Mortality % 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 PHYSIOLOGICAL APPROACH DOSES SHOULD BE MAXIMUM TOLERATED DOSES SHOULD BE MAXIMUM TOLERATED IN CHF, TWICE A DAY (CAPTOPRIL 3-4 TIMES/DAY) IN CHF, TWICE A DAY (CAPTOPRIL 3-4 TIMES/DAY) IDEAL BLOOD PRESSURE OFTEN <100 mmHg IF NO POSTURAL SYMPTOMS IDEAL BLOOD PRESSURE OFTEN <100 mmHg IF NO POSTURAL SYMPTOMS IF CHF WORSE AND HYPOTENSIVE, DON’T REDUCE THE DOSE UNLESS CLEARLY NECESSARY IF CHF WORSE AND HYPOTENSIVE, DON’T REDUCE THE DOSE UNLESS CLEARLY NECESSARY KEEP PATIENT ON IT DESPITE MINOR INCREASES IN CREATININE OR POTASSIUM KEEP PATIENT ON IT DESPITE MINOR INCREASES IN CREATININE OR POTASSIUM

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

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. Carvedilol Causes a Dose-Related Improvement in LV Ejection Fraction p<0.0001 ** * * 8 7 6 5 4 3 2 1 0 Placebo 6.25 mg12.5 mg25 mg bid *p<0.005 vs. placebo **p<0.0001 vs. placebo LVEF Circulation 1996;94:2807-2816 Carvedilol

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 01 - 23 - 45 - 611 - 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