CURRENT APPROACH TO THE TREATMENT OF CONGESTIVE HEART

FAILURE

Treatment of CHF in 1970

• Digitalis• Diuretics• Salt restriction

Modern Rx of CHF

• Diuretics• Vasodilators• Beta-blockers• Inotropic agents

• Digoxin• Adrenergic agents• Milrinone

• Aldactone• BiV Pacing

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

Digitalis: Effect on Hospitalizations

Digoxin Placebo

67.1%

64.3%

Hos

pita

lizat

ions

(%)

N Engl J Med 1997;336:525-533

Digitalis: Effect on Mortality

Digoxin Placebo

35.1%34.8%

0

40M

orta

lity

%

N Engl J Med 1997;336:525-533

“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

CLINICAL ASSESSMENT OF CHF

• BLOOD PRESSURE • JVP• RALES• EDEMA• SERUM CREATININE• MITRAL REGURGITATION• POSTURAL SYMPTOMS• BNP

WHAT TO EXPECT FROM DIURETICS

• RAPID RESPONSE• DECREASED FILLING PRESSURES• EDEMA BUT the tendency is for• CARDIAC OUTPUT • CREATININE • NEUROHUMORAL ACTIVATION

VASODILATORS

• NITRATES• VENOUS• ARTERIOLAR

• ARTERIAL DILATORS• HYDRALAZINE

• BALANCED VASODILATORS• NITROPRUSSIDE• ACE INHIBITORS• ANGIOTENSIN RECEPTOR BLOCKERS• OMEPATRILAT (combined ACEI and NEP)

WHAT TO EXPECT FROM VASODILATORS

• FILLING PRESSURES• CARDIAC OUTPUT• EXERCISE TOLERANCE• NEUROHUMORAL ACTIVATION• REVERSE REMODELING• HOSPITALIZATIONS and MORTALITY

HOW TO USE ACE INHIBITORSHOW TO USE ACE INHIBITORS

• PHYSIOLOGICAL APPROACHPHYSIOLOGICAL APPROACH

• DOSES SHOULD BE MAXIMUM TOLERATEDDOSES 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 IDEAL BLOOD PRESSURE OFTEN <100 mmHg IF NO POSTURAL SYMPTOMSPOSTURAL SYMPTOMS

• IF CHF WORSE AND HYPOTENSIVE, DON’T REDUCE IF CHF WORSE AND HYPOTENSIVE, DON’T REDUCE THE DOSE UNLESS CLEARLY NECESSARYTHE DOSE UNLESS CLEARLY NECESSARY

• KEEP PATIENT ON IT DESPITE MINOR INCREASES IN KEEP PATIENT ON IT DESPITE MINOR INCREASES IN CREATININE OR POTASSIUMCREATININE OR POTASSIUM

-30%

-25%

-20%

-15%

-10%

-5%

0%

8 % p=0.12 12%

p=0.002

Risk of all cause Risk of all cause mortalitymortality

Risk of death or Risk of death or hospitalizationhospitalization

Frequency of HF Frequency of HF hospitalizationshospitalizations

25%p=0.002%

Dec

reas

eATLAS (high vs low dose lisinopril)

WHAT TO EXPECT OF NITRATES

• VENODILATATION AT LOW DOSES• ARTERIAL DILATATION AT HIGH DOSES• CARDIAC OUTPUT• MITRAL REGURGITATION • BENEFICIAL REMODELING• IMPROVED EXERCISE TOLERANCE

DRUG COMBINATIONS

• ACE INHIBITORS AND NITRATES• ACE INHIBITORS AND ANGIOTENSIN

RECEPTOR BLOCKERS• BETA-BLOCKERS• ALDACTONE• HYDRALAZINE• INOTROPES

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

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

US CARVEDILOL TRIAL

MILD MOD DOSE-RES SEVERE

MO

RTA

LITY

(%)

0

10

20

30

40

R.R. .50 .61 .67 .41

25

35

21

32

21

29

1113

Carvedilol Causes a Dose-Related Improvement in LV Ejection Fraction

p<0.0001 **

**

8

7

6

5

4

3

210

Placebo6.25 mg 12.5 mg 25 mg bid

*p<0.005 vs. placebo

**p<0.0001 vs. placebo

LVE

F

Circulation 1996;94:2807-2816

Carvedilol

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

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

Time course of effects Beta-Blockade Therapy

Clinical Benefit

Clinical Deterioration

0 1 - 2 3 - 4 5 - 6 11 - 12

MonthsAm J Cardiol 1997;79:794-798

Recommended Monitoring During Titration of Beta-Blocker Therapy

• Symptoms• Weight• Heart rate (rhythm)• Blood pressure• Jugular venous

pressure• Lung auscultation

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

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

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.

JVP Elevated

If BP low, consider adding anitrate (diuretic often but not always necessary).

If blood pressure ok, increase ACE/add nitrate. Fine tune with diuretic when necessary.

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.

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.

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).

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.

Another approach is to view this as anopportunity to improve his therapy by:

• Increasing vasodilators

• ?Reduce diuretics

• ?Combine vasodilators

• Add beta-blocker

• Add aldosterone antagonist

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

You could just give more diuretic.What will happen?

or

You could manipulate the vasodilators And possibly reduce the diuretics.

Case Study

Same patient but the JVP is low and the BP is 80/60 mmHg.

What would you do?

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