Download CHF

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
Hospitalizations (%)
Digitalis: Effect on Hospitalizations
67.1%
64.3%
Digoxin
Placebo
N Engl J Med 1997;336:525-533
Digitalis: Effect on Mortality
Mortality %
40
34.8%
0
Digoxin
35.1%
Placebo
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 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
ATLAS (high vs low dose lisinopril)
% Decrease
0%
-5%
-10%
-15%
-20%
-25%
-30%
Risk of all cause Risk of death or Frequency of HF
mortality
hospitalization hospitalizations
8%
p=0.12
12%
p=0.002
25%
p=0.002
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
40
35
32
29
MORTALITY (%)
30
25
21
21
20
13
11
10
0
R.R.
MILD
.50
MOD
.61
DOSE-RES SEVERE
.67
.41
LVEF
Carvedilol Causes a Dose-Related
Improvement in LV Ejection Fraction
8
*p<0.005 vs. placebo
7
**p<0.0001 vs. placebo
**
p<0.0001
*
6
*
5
4
3
2
1
0
6.25 mg
Placebo
12.5 mg
25 mg bid
Carvedilol
Circulation 1996;94:2807-2816
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
Months
Am 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 a
nitrate (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 an
opportunity 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