Transcript CHF and SuperHeroes

Artwork
by
Aaron Jameson
Cast of Characters
Plan of Attack
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Importance
Evaluate a Case
Explain the Pathophysiology
Develop the Armamentarium
– Why they work
– How to monitor

Cover the important evidence for
each group
CHF and Super Heroes
The Role of
Rx Man
Surgeon General’s Warning

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This lecture will require you to write
some things down
You could develop carpal tunnel
syndrome
You could develop an irreversible
hand cramp
You could retain something longer
than 5 minutes
A Fatal Choice

You can have a cancer that:
kills 40% of people in 5 years
OR
 You
can have your first episode
of symptomatic CHF
Did You Choose CHF?
OOPS !!
Epidemiology
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
CHF Kills A LOT of People
CHF Makes A LOT of People’s lives
miserable
CHF costs a WHOLE LOT of $
New York Heart
Association
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Class
Class
Class
Class
I
II
III
IV
New Approach to the Classification
of Heart Failure
A
B
C
D
Stage
High risk for
developing heart
failure (HF)
Asymptomatic HF
Patient Description
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Symptomatic HF
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Refractory
end-stage HF
Hunt SA et al. J Am Coll Cardiol. 2001;38:2101–2113.
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Hypertension
CAD
Diabetes mellitus
Family history of cardiomyopathy
Previous MI
LV systolic dysfunction
Asymptomatic valvular disease
Known structural heart disease
Shortness of breath and fatigue
Reduced exercise tolerance
Marked symptoms at rest despite
maximal medical therapy (eg, those
who are recurrently hospitalized or
cannot be safely discharged from
the hospital without specialized
interventions)
Classification of HF: Comparison
Between ACC/AHA HF Stage and
NYHA Functional Class
ACC/AHA HF Stage
A At high risk for heart failure
but without structural heart
disease or symptoms of heart
failure (eg, patients with
hypertension or coronary artery
2113.
disease)
B Structural heart disease but
without symptoms of heart
failure
C Structural heart disease with
prior or current symptoms of
heart failure
D Refractory heart failure
requiring specialized interventions
Hunt SA et al. J Am Coll Cardiol. 2001;38:2101–2113.
NYHA Functional Class
None
I
Asymptomatic
II Symptomatic with moderate
exertion
III
Symptomatic with minimal
IV Symptomatic
at rest
exertion
Penelope
A 74 year old white female
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5 feet tall
160 pounds
S/P CVA
Hx mild CHF , HTN and DM 2
Penelope : Episode 1
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Admitted to ER with Acute SOB.
Auscultation reveals crackles 1/2
way up on both sides
CXR shows mild interstitial
infiltrates
BP: 150/80
2+ pitting edema
Penelope : Episode 1
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Admitted to ER with Acute SOB.
Auscultation reveals crackles 1/2
way up on both sides
CXR shows mild interstitial
infiltrates
BP: 150/80
2+ pitting edema
NYHA class?
Penelope
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Drugs:
Insulin
Dyazide daily
Zestril 5 mg daily
Penelope is tied to the
railroad tracks
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You can save her from floods
You can give her a pillow and make
her more comfortable
You can even delay the train
But you can’t take her off the
tracks.
Circulation Review
Preload
Afterload
High
pressure
Low
pressure
Famous Last Words

Everything that can be invented has
been invented.”
--Charles H. Duell,
Commissioner,
U. S. Office of Patents, 1899.
Systolic vs. Diastolic
Dysfunction
Normal Heart
120 ml
Normal Heart
EF
EF70/120
70/120
58
58 %
%
120 ml
70ml
CO = 70ml /beat * 72/min=5040 ml/min
Systolic Dysfunction
160 ml
Systolic Dysfunction
160 ml
EF
EF40/160
70/120
25
58 %
%
40ml
CO = 40ml /beat * 72/min=2880 ml/min
Diastolic Dysfunction
57 ml
Diastolic Dysfunction
EF
EF 40/57
70/120
70%
58 %
57 ml
40ml
CO 40ml / beat * 72/min =2880 ml/min
Diastolic Heart Failure
and Intravascular
Congestion
Describe Diastolic Dysfunction
Other Neuroendocrine mediators

Arginine Vasopressin (ADH)

Stimulated by extreme low kidney perfusion, just like
Aldosterone. Causes free water retention and hyponatremia
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Endothelin
One of the absolute most potent vasoconstrictors.
Endothelin antagonists in the works

Atrial and B-type Natriuretic peptide
Stimulated by stretch of the atria and the ventricles and
cause sodium and water excretion. Sort like a counterregulatory hormone to aldosterone
CHF: Compensation
Cardiac Output
Cardiac
Output
(Compensated)
SNS
Kidney
Perfusion
Preload
Na+ & H2O
retention
Renin
Angiotensin
Aldosterone
CHF: Compensation
Cardiac Output
CHF: Compensation
Cardiac Output
Kidney
Perfusion
CHF: Compensation
Cardiac Output
Kidney
Perfusion
Renin
Angiotensin
Aldosterone
CHF: Compensation
Cardiac Output
Kidney
Perfusion
Na+ and H2O
retention
Renin
Angiotensin
Aldosterone
CHF: Compensation
Cardiac Output
Kidney
Perfusion
Preload
Na+ and H2O
retention
Renin
Angiotensin
Aldosterone
CHF: Compensation
Cardiac
Output
Cardiac Output
(Compensated)
Kidney
Perfusion
Preload
Na+ and H2O
retention
Renin
Angiotensin
Aldosterone
CHF: Compensation
Cardiac
Output
Cardiac Output
(Compensated)
Kidney
Perfusion
Preload
Na+ and H2O
retention
Renin
Angiotensin
Aldosterone
CHF: Compensation
Cardiac
Output
Cardiac Output
(Compensated)
Preload
Na+ and H2O
retention
SNS
Kidney
Perfusion
Renin
Angiotensin
Aldosterone
CHF: Warning: New Slide!
Cardiac Output
WHY?
CHF: Warning: New Slide!
Cardiac Output
WHY?
Systolic
Dilated
Cardiomyopathy
CAD
HTN
CHF: Warning: New Slide!
Cardiac Output
WHY?
Diastolic
Hypertension
CAD
Hypertrophic
Cardiomyopathy
Systolic
Dilated
Cardiomyopathy
CAD
HTN
God is
Dead
Another famous last quote
Nieztsche 1885
Nieztsche is
Dead
God
2007
CHF: The Viscious Cycle
Cardiac Output
Kidney
Perfusion
Renin
Angiotensin
Aldosterone
CHF: The Viscious Cycle
Cardiac Output
Vasoconstriction
SNS
Kidney
Perfusion
Renin
Angiotensin
Aldosterone
CHF: The Viscious Cycle
Cardiac Output
Afterload
Vasoconstriction
SNS
Kidney
Perfusion
Renin
Angiotensin
Aldosterone
High Pressure
Left Ventricle
Arteries
High Pressure: Vasoconstriction
Left Ventricle
Arteries
CHF: The Viscious Cycle
Cardiac Output
Kidney
Perfusion
Renin
Angiotensin
Aldosterone
CHF: The Vicious Cycle
Cardiac Output
Kidney
Perfusion
Na+ and H2O
retention
Renin
Angiotensin
Aldosterone
CHF: Vicious Cycle
Cardiac Output
Preload and
Pulmonary Edema
Na+ and H2O
retention
Kidney
Perfusion
Renin
Angiotensin
Aldosterone
CHF: Vicious Cycle
Strain
Cardiac Output
Preload and
Pulmonary Edema
Na+ and H2O
retention
Kidney
Perfusion
Renin
Angiotensin
Aldosterone
CHF: Symptoms
Strain
Cardiac Output
Fluid Overload
Preload and
Pulmonary Edema
Na+ and H2O
retention
Low Perfusion
Kidney
Perfusion
Renin
Angiotensin
Aldosterone
CHF Pharmacotherapy

New Drugs
Mechanism(s)
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Monitoring for Efficacy
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Monitoring for Adverse Effects
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Back to Penelope: Episode 1
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Admitted to ER with Acute SOB.
Auscultation reveals crackles 1/2
way up on both sides
CXR shows mild interstitial
infiltrates
BP: 150/80
2+ pitting edema
This is a
Job for...
Water Boy
Diuretics: Mechanism
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Sodium and Water Excretion
Preload
Necessary Poison
Fluid Overload
Pulmonary Edema
Low perfusion
Loss of Renal Function
Fluid Overload
Pulmonary Edema
Low perfusion
Loss of Renal Function
Low perfusion
Loss of Renal Function
Fluid Overload
Pulmonary Edema
Diuretics: Efficacy
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~1 Kg / day (short term)
~1000 mls net loss / day
700 mls insensible loss (output)
Lung Sounds / CXR
Decreased Edema
Diuretics: Efficacy
Example:
Input: IV at 100ml/hour
Output: 2700 ml in 24 hours
Net:
Don’t forget 700ml insensible + 300ml =
1000ml lost
Diuretic Dosing
Short Term:
The Nike Rule
Long Term:
Be a Sissy.
Diuretics:
Loops
Thiazides vs Loops
torsemide vs furosemide
Absorption, duration and Cost
Other loops
Potency vs efficacy
Diuretics: Side Effects
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BUN / Cr Ratio
Potassium
Do Orthostatics !!
Clinical Hydration Status
Glucose
Uric Acid
Ca++
Penelope : Episode 1
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
Admitted to ER with Acute SOB.
Auscultation reveals crackles 1/2
way up on both sides
CXR shows mild interstitial
infiltrates
BP:
BP 150/80
150/80
2+ pitting edema
Which rule should we use? Nike or Sissy?
Penelope : Episode 1

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

Admitted to ER with Acute SOB.
Auscultation reveals crackles 1/2
way up on both sides
CXR shows mild interstitial
infiltrates
BP:
BP 150/80
150/80
2+ pitting edema
What about the Zestril dose?
ACE of Hearts
Angiotensinogen
Renin
Angiotensin I
COW HERE
Angiotensinogen
Renin
Angiotensin I
Angiotensin I
Angiotensinogen
Renin
ACE
Angiotensin II
Angiotensin I
Angiotensinogen
Renin
ACE
Angiotensin II
Na+
Retained
Aldosterone
K+ Lost
Vasoconstriction
Angiotensin I
Angiotensinogen
Renin
ACE
ACE I
Angiotensin II
Aldosterone
Aldosterone
K+ Retained
Vasoconstriction
Angiotensin I
Angiotensinogen
Renin
ACE
Kinins
Kinins
ACE I
Angiotensin II
Aldosterone
Breakdown
Vasoconstriction
OK,
So how does this benefit
the fluid overloaded,
under-perfused
CHF patient
insert preload diagram here
Whew !!!
I Can Breathe !!
Low
Pressure
High Pressure: Afterload
Left Ventricle
Arteries
High Pressure: Post Dilation
Left Ventricle
Arteries
OK,
So how does this benefit
the fluid overloaded,
under-perfused
CHF patient
Ace Inhibitors: Efficacy
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Breathing and fluid
improved
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Exercise capacity improved
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Mental Status Improved
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B. P.
Ace I: Adverse Effects
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BUN / Creatinine
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Potassium
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Hypotension (dizziness)
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Cough
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Angioedema
ACE & Kidneys
Ace Inhibitors:Warning Signs
Impaired Renal Perfusion
 Diuretic
 CHF
– Especially w/ Hyponatremia
 Ascites
Ace Inhibitors : Dosing
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CHF vs HTN
Caution: Hyponatremia
Ace Inhibitors :
Drug Intx
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Potassium Sparing Diuretics
NSAIDS
What is the intx with ACE Inhibitors and NSAIDS?
V-HeFT I
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Enalapril vs. Placebo
Class II & III
Mortality
– 34.3 vs 25.6 @ 2 years NNT
– 53.6 vs 49.7 @ 4 years NNT
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(benefit diminishes w/ time)
11.5
25.6
CONSENSUS I
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Class IV
Mortality at one year
52% vs 36%
NNT 6 !!!
Average dose 18.4 mg /day
SOLVD-Treatment
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Class II & III
Mortality at 4 years
39.7 % vs 35.2 %
NNT 22
Mean daily dose of enalapril= 16.6 mg
Penelope :
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Increase Zestril to 10 mg daily
Because :
 Ace
Inhibitors Save Lives
Penelope : Episode 2
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One month later…
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Develops an intractable cough
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Your questions?
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Your recommendation?
Angiotensin I
Angiotensinogen
Renin
Kinins
Chymase
Angiotensin II
Breakdown
Na+
Aldosterone
Aldosterone
K+ Retained
Vasoconstriction
Vasoconstriction
AT3
AT4
AT2
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Feedback
Fetal effects
Many others
Angiotensin II II
Angiotensin
AT1
Aldosterone
AT1
Vasoconstriction
ARBs
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Similar to ACE inhibitors but also
many differences
Highly variable half lives
Highly variable AT1 receptor
affinity
RESOLVD
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Candesartan vs. candesartan +enalapril
vs. enalapril alone
Class II – IV
Terminated early due to candesartan
groups doing worse.
Difficult to interpret due to unusually
low mortality and morbidity in enalapril
group
RESOLVD
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Because the study wasn’t powered to show
mortality, the authors conclusion didn’t
mention higher mortality in the
candesartan groups!
“Candesartan was as effective, safe, and
tolerable as enalapril”
“The Combination… was more beneficial for
preventing left ventricular remodeling”
Elite II
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Losartan 50mg / d vs. placebo
Class III & IV
Mortality: No difference
ValHeft
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Valsartan
Class II-IV
Some benefit added to ACE OR to
a Beta Blocker
INCREASED MORTALITY
When added to both !!
CHARM (as in snake?)
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Alternative
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Added
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Preserved
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Overall
– In ACE intolerant patients
– Improved outcomes
moderately
– Improved outcomes
minimally
– Beta blocker would be
better (opinion)
– No statistical
improvement
– Statistical improvement
Penelope
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Cozaar 50mg daily
Continue Lasix etc.
Penelope:
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Episode 3
Four months later…
There has been trouble getting
weights in the nursing home
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Another episode of SOB,
02 saturation 85%
Weight 178 pounds
BUN / Cr: 40 / 1.4
Penelope
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Treatment now?
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Right Again!
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Treatment: Lasix 80 mg BID
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What will that do to the BUN / Cr?
Vitamin L
Penelope:
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Two weeks later…
Wt. 175 pounds
Breathing improved but not good
No CXR or ausculation
BUN / Cr 50 / 1.5
What do you recommend ?
My Momma Always Said:
Patience is
a Virtue
Penelope
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Weight decreases to 158 over the
next 2 months.
Breathing greatly improved in the
last month.
BP: 110 / 70
Guesses on the BUN and Creat??
90 / 2.0
Penelope: Episode 5
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What next??
Decline in mental status. Sleeping
18 to 20 hours per day. Confused,
wild delusions.
What do you do now?
The Hemodynamic Duo!!
Nitrates / Hydralazine:
Mechanisms
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Hemodynamic effects similar to Ace
Inhibitors
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Nitrates decrease Preload
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Hydralazine decreases afterload
Nitrates / Hydralazine
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PERHAPS a little:
– less mortality benefit
– more symptom benefit
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Less renal impairment risk
Nitrates / Hydralazine:
Efficacy
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Similar to Ace Inhibitors
Better in African Americans?
Nitrates / Hydralazine:
Adverse Effects
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P.O.S. (Pill overload syndrome)
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Headache
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Nausea
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Hypotension
Nitrates / Hydralazine:
BIDIL®
Could we use digoxin?
Digimon
Digoxin: Mechanisms
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Increased force of contraction
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Decreased hospitalizations
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No mortality benefit or harm
Digoxin: Efficacy
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Urine Output

Mental Status
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Exercise capacity improved
Digoxin:
Adverse Effects
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Potassium
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Mental Status
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Pulse / EKG

Nausea / Vomiting
Digoxin: Evidence
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The Dig Trial
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No difference in mortality
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67.1% vs 64.3% hospitalization
1% vs 2 % hospitalized for
suspected dig toxicity
Digoxin Pharmacology? Clinical Effect?
Meanwhile, Penelope is still
on the Railroad Tracks
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Increase Cozaar
BUN goes to 120 (oops)
Decrease Cozaar
Add Hydralazine and Nitrates
Titrate up to 50 mg TID and 20
mg TID
Penelope
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Result?
Somnolence improves
Delusions resolve
BUN / Cr 80 / 1.8
Weight 158
BP: 100/60
Add a beta blocker?
Sir Blocksalot
Adrenergic Receptors in
Normal vs Failing Left
Ventricles
80
1
2
Receptor density (fmol/mg
protein)
70
60
50
*P<.05
vs normal function
40
1
*
30
20
10
0
Mean + SD.
Normal function (n=12)
Cardiomyopathy (n=54)
1: 2 80%:20%
1: 2 65%:35%
Adapted from Bristow M. J Am Coll Cardiol. 1993;22(4 Suppl A):61A–71A.
Beta Blockers
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Improve Cardiac Function ??

Decreased Mortality

Don’t Use Unless CHF is stable
 Beta
Blockers Block Death
Beta Blockers: MERIT-HF
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Metoprolol XL
Mostly Class II & III
Mortality over one year
– 11% vs. 7.2%
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NNT 26
Dosing
Beta Blockers:Carvedilol Trial
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Mostly Class II & III
Mortality over 6 months
– 3.2% vs. 7.8%
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NNT 21
hospitalization 14% vs 19%
NNT 20
2% died or deteriorated during run in
Which beta blockers are proven in CHF?
Penelope
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She does well for 3 months

Penelope died July 9, 1998
Penelope
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What do we know now that we
didn’t know then?
Spiro the Super Mouse
CHF: Vicious Cycle
Strain
Cardiac Output
Preload and
Pulmonary Edema
Na+ and H2O
retention
Kidney
Perfusion
Renin
Angiotensin
Aldosterone
Aldosterone
Aldosterone
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Sodium Retention
Magnesium and Potassium Loss
Sympathetic Activation
Parasympathetic Inhibition
Myocardial fibrosis
Vascular Fibrosis
Impairs arterial compliance
RALES
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Spironolactone 25 mg / d vs. Placebo
Class III & IV

Mortality at 11 months (stopped early)
46% vs 35 %

NNT: 9

Newbies


Tezosentan endothelin receptor
antagonist Who knows
Levosimendan Calcium sensitizer on
troponin C may increase force of
contraction without increasing
myocardial oxygen consumption.
Nesiritide - Origin
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Stretch receptors in the Atria (ANP)
and the Ventricles (BNP)
Cause natriuresis and vasodilation
Makes perfect sense
Easy to Market
Benefit??
Nesiritide
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This is also known as BNP and causes
diuresis and vasodilation.
Studies show it superior to placebo
and equal to conventional therapy.
If you don’t count mortality
It costs about $1 million per dose,
may be useful in highly specific cases
Nesiritide – On the Other Hand
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BNP is a good test in diagnosing CHF
<100 mcg/ml NOT CHF
101 to 999
NOT normal, but
probably not CHF
1000 to 4000 CHF or related condition
>4000
almost certainly CHF
Seven Roles for Rx Man
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Sell them a scale
Poke at their ankles
Ensure labs (K+)
Teach them to take their pulse
NSAIDS
Salt Police
Cough Syrup patrol
Clinical Signs and Sx of CHF
Fluid Overload
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Shortness of Breath
DOE
Orthopnea / PND
Pedal Edema
CXR
Clinical Signs and Sx of CHF
Inadequate Perfusion
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Decreased Urine Output
Increased BUN/Cr ratio
Impaired Mental Status
Cool, Clammy Skin
Fatigue
Recap: AHA/ACC Heart
Failure Guidelines
J Heart Lung Transplant Feb, 2005

Class I Recommendations
– Diuretics for patients with fluid retention (A)
– ACEI for all patients unless contraindicated (A)
– Beta-blockers for all stable patients unless
contraindicated (A)
– Digitalis for treatment of symptoms (A)
– Withdrawal of drugs that may adverse the
status of heart failure patients (NSAIDs, most
antiarrhythmics, most calcium channel blockers)
(B)
Recap: AHA/ACC Heart
Failure Guidelines
J Heart Lung Transplant Feb, 2005

Class I Recommendations (cont’d)
• Exercise training
• Implantable defibrillator if history of
arrest, V Fib or bad V. Tach
• Resynchronization therapy where indicated
Recap: AHA/ACC Heart
Failure Guidelines
J Heart Lung Transplant Feb, 2005

Class IIa Recommendations (conflicting evidence/opinion
but evidence favors)
– Spironolactone for recent Class IV symptoms (B)
– ARBs for patients not tolerating ACEI due to cough or
angioedema (A)
– Combination of hydralazine + nitrate in patients not an ACEI
candidate due to hypotension/renal insufficiency (B)
• Digitalis for treatment of symptoms (A)
• Use of a CCB with negative inotropic effect may be harmful low
ejection fraction (A)

Class IIb Recommendations (conflicting evidence/opinion
with less evidence to support)
– Addition of an ARB to an ACEI (B)
– Addition of nitrate +/- hydralazine to patients on ACEI (B)
Recap: AHA/ACC Heart
Failure Guidelines
J Heart Lung Transplant Feb, 2002

Class III Recommendations (no data or
harmful)
– Intermittent IV positive inotropes (C)
– ARB instead of an ACEI in patients never tried
on or could tolerate an ACEI (B)
– Use of an ARB before beta-blocker in a patient
on an ACEI
– Use of a CCB to treat CHF (B)
– Routine use of nutritional supplements (CoQ10,
etc.) or hormones (thyroid, growth) (C)
Case #1

KK is a 71 year old male with known
history of CHF admitted for
hypotension and shortness of
breath
Case #1
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Albuterol
Ipratropium
Phenytoin
Neurontin
Levothyroxine
Protonix
Lasix 20mg /day
Amiodarone
Verapamil 240mg/day
Labs
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
BNP 995
Troponin <0.3
LDL <100
Na 137
K
4.1
Cl
101
TCO2 29
BUN 33
Creat 1.3
x 3
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Weight on admission= 84 kg
BP 102/63
Heart Rate 58
TSH 2.2
#1 Monitoring Parameter?
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84 Kg on admission
Day 1: 83.5
Day 2: 83.3
Day 3: 83.1
Case #1