CURRENT APPROACH TO THE TREATMENT OF CONGESTIVE HEART FAILURE

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CURRENT APPROACH TO THE TREATMENT OF CONGESTIVE
HEART FAILURE
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Treatment of CHF in 1970

• Digitalis
• Diuretics
• Salt restriction

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Modern Rx of CHF

• Diuretics
• Vasodilators
• Beta-blockers
• Inotropic agents
• Digoxin
• Adrenergic agents
• Milrinone
• Aldactone
• BiV Pacing

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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

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Digitalis Effect on Hospitalizations
67.1
64.3
Hospitalizations ()
Digoxin
Placebo
N Engl J Med 1997336525-533
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Digitalis Effect on Mortality
40
35.1
34.8
Mortality
0
Digoxin
Placebo
N Engl J Med 1997336525-533
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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

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CLINICAL ASSESSMENT OF CHF

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

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WHAT TO EXPECT FROM DIURETICS

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

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VASODILATORS

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

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WHAT TO EXPECT FROM VASODILATORS

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

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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 lt100 mmHg IF NO
  POSTURAL SYMPTOMS
• IF CHF WORSE AND HYPOTENSIVE, DONT REDUCE THE
  DOSE UNLESS CLEARLY NECESSARY
• KEEP PATIENT ON IT DESPITE MINOR INCREASES IN
  CREATININE OR POTASSIUM

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ATLAS (high vs low dose lisinopril)
Risk of all cause mortality
Risk of death or hospitalization
Frequency of HF hospitalizations
8 p0.12
12 p0.002
Decrease
25 p0.002
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WHAT TO EXPECT OF NITRATES

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

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DRUG COMBINATIONS

• ACE INHIBITORS AND NITRATES
• ACE INHIBITORS AND ANGIOTENSIN RECEPTOR BLOCKERS
• BETA-BLOCKERS
• ALDACTONE
• HYDRALAZINE
• INOTROPES

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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

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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

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US CARVEDILOL TRIAL
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Carvedilol Causes a Dose-Related Improvement in
LV Ejection Fraction

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plt0.005 vs. placebo plt0.0001 vs. placebo
plt0.0001
7

6

5
4
3
2
1
0
6.25 mg
12.5 mg
25 mg bid
Placebo
Carvedilol
Circulation 1996942807-2816
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Beta-Blockers Patient Selection

• Stable Class I-IV patients
• LVEF lt 35 - 40
• Ischemic or non-ischemic
• On ACE inhibitor, diuretics, with or without
  digoxin
• Heart Rate gt 60 bpm, no high degree a-v block
• Systolic BP gt 85 - 90 mmHg
• No contraindications to beta-blockade

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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

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Time course of effects Beta-Blockade Therapy

Clinical Benefit
Clinical Deterioration
0
1 - 2
3 - 4
5 - 6
11 - 12
Months
Am J Cardiol 199779794-798
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Recommended Monitoring During Titration of
Beta-Blocker Therapy

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

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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

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General Approach to Rx

• Look for precipitating cause
• B.P, JVP and Creatinine central to assessment
  and monitoring
• A quick fix probably wont work as well as
  re-optimizing Rx
• Follow up is usually essential

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Blood pressure

• BP 90-100 well-tolerated. Some tolerate 70.
• If asymptomatic, dont 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.

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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.
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Creatinine Increasing

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

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• If a patient deteriorates on vasodilators
• and beta-blockers
• dont 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.

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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).

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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.
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• 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

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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

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

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

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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