Download Strength of Evidence = A

Heart Failure
---
HFSA 2010 Practice Guideline ---
清泉醫院 柯國銓
2012.03.06
錢非萬能，沒錢萬萬不能。
Guideline非萬能，
沒Guideline萬萬不能。
HFSA 2010 Comprehensive Heart Failure Practice Guideline
Strength of Recommendation


“Is recommended”
“Should be
considered”

Part of routine care
» Exceptions should be
minimized

Majority of patients
should receive
intervention
» Some discretion allowed

“May be considered”

“Is not
recommended”
Individualization of
therapy is indicated
 Therapy should not be
used

Number 1 Killer
>65years
Leading cause of hospitalization
1-2%
of Health Care cost
$ 39.2 Billion
5 years from diagnosis
only 50% alive
In 1950
first edition of Harrison’s Principles of Internal Medicine
Decubitus
Dietary sodium restriction
Digitalis
Diuretics (mercurial)
Venesection and
Morphine
The Management of Heart Failure: The Past, the Present, and the Future Eugene Braunwald,MD
Circulation: Heart Failure. 2008;1:58-62
In 1970
Sixth edition of Harrison’s Principles of Internal Medicine
Diuretics (Thiazide, Loop, Potassium sparing)
β-adrenergic agonist
Precipitating cause
The Management of Heart Failure: The Past, the Present, and the Future Eugene Braunwald,MD
Circulation: Heart Failure. 2008;1:58-62
OPT: Optimal Pharmacologic Therapy
SPIRONOLACTONE
DIGOXIN
DIURETICS
BETA BLOCKERS
ACE INHIBITORS or ARB
ADJUNCT: HYDRALAZINE and NITRATES
ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult. 2001; 1-56.
Management of heart failure over
the past 40 years
Katz, A. M. Circ Heart Fail 2008;1:63-71
Copyright ©2008 American Heart Association
What Causes Heart Failure?
Factors contributing to CHF
♥ Coronary Artery Disease : most prevalent
♥ Ischemic Heart Disease
♥ CAD: Myocardial Infarct
♥ Untreated High Blood Pressure
♥ Faulty Heart Valves
♥ Cardiomyopathy
♥ Cardiac Arrhythmia
♥ Lung Disease
♥ Diabetes
♥ Infections
♥ Alcoholism
♥ Toxic Drugs
♥ Severe Anemia
♥ Hyperthyroidism
ACC/AHA Heart Failure Stages
Stage Description
A Patients without structural heart disease but at increased risk to
develop heart failure.
B Patients with structural heart disease but no heart failure
symptoms.
C Patients with structural heart disease with past or current heart
failure symptoms . Correlates with NYHA Heart Failure Class I,
II, and III.
D Patients with refractory end-stage heart failure (heart failure
symptoms at rest despite maximal medical therapy). Correlates
with NYHA Heart Failure Class IV.
HFSA 2010 Practice Guideline (3.2)
HF Risk Factor Treatment Goals
Risk Factor
Goal
Hypertension
Generally < 130/80
Diabetes
See ADA guidelines1
Hyperlipidemia
See NCEP guidelines2
Inactivity
20-30 min. aerobic 3-5 x wk.
Obesity
Weight reduction < 30 BMI
Alcohol
Men ≤ 2 drinks/day, women ≤ 1
Smoking
Cessation
Dietary Sodium
Maximum 2-3 g/day
1Diabetes
2JAMA
Adapted from:
Care 2006; 29: S4-S42
2001; 285:2486-97
Treating Hypertension
to Prevent HF
 Aggressive
blood
pressure control:
Decreases
risk of
new HF
by ~ 50%
56% in DM2
Lancet 1991;338:1281-5 (STOP-Hypertension
JAMA 1997;278:212-6 (SHEP)
UKPDS Group. UKPDS 38. BMJ 1998;317:703-713
 Aggressive
BP
control in
patients with
prior MI:
Decreases
risk of
new HF
by ~ 80%
Heart Failure
Inability of heart to pump blood
out as rapidly as it enters
Often referred to as congestive
heart failure (CHF)
Congestive Heart Failure
Congestion of pulmonary or
systemic circulation
(backward failure)
Reduced output to body
tissues (forward failure)
2 Types of Heart Failure
Systolic
Dysfunction
Diastolic
Dysfunction
(Contraction) 2/3 of Patients
(Relaxation)
♥ The heart
♥ Chambers don’t
fill up so less
blood goes to the
lungs and body
♥ Stiff heart muscle
can’t relax
♥ Not enough blood
fills the chambers
becomes weak and
enlarged
♥ The weakened
heart muscle can’t
contract
♥ Not enough blood
is pumped from
the chambers
Figure 11.1. Diagnostic Criteria:
HF with Reduced vs. HF with Preserved EF
Clinical evidence of HF:
Clear clinical presentation of HF
LVEF ≥ 50%
LVEF < 50%
Supportive evidence:
Supportive evidence:
Eccentric LVH or remodeling
Concentric LVH or remodeling
Exclusions: Non-myocardial disease
Left atrial enlargement in
absence of AF
Echo Doppler or catheter
evidence of diastolic dysfunction
Exclusions: Non-myocardial
disease
Adapted from Yturralde FR. Prog
Cardiovasc Dis 2005;47:314-19
Figure 11.2. Etiology of HF with Reduced vs. HF with
Preserved LVEF
HF with Reduced
EF
NonMyocardiala
Myocardialb
Hypertension
CAD
Valvular
disease AS,
AR, MR,
MS
High output
Anemia,
AV fistula
Diabetes
HF with Preserved EF
NonMyocardiala
Valvular
disease
AS, AR,
MR, MS
Cardiomyopathy
genetic,
postpartum, viral,
drug/radiation
Infiltrative
myopathyc
Myocardialb
Hypertension
CAD
Diabetes
Cardiomyopathy
Pericardial
constraint
constriction,
tamponade
High output
Anemia,
AV fistula
genetic,
postpartum, viral,
drug/radiation
Infiltrative
myopathyc
CHF
May develop acutely or may
be a chronic disease
Chronic CHF may worsen
acutely
Congestive Heart Failure
Left sided
Right sided
Biventricular
Left-Sided Heart Failure
Increase
pressure in
pulmonary capillaries forces
blood serum out of capillaries
into interstitial spaces and
alveoli
Increase respiratory work and
decrease gas exchange occur
Left Heart Failure Symptoms
Dyspnea
on exertion(FcI, II,III)
Paroxysmal nocturnal dyspnea
(FcIV)
Orthopnea(FcIV)
Fatigue, generalized weakness
New York Heart Association (NYHA) Functional
Classification
Class I Ordinary physical activity does not cause undue fatigue,
Fc I
palpitation or dyspnea (shortness of breath).
Class II Comfortable at rest, but ordinary physical activity
Fc II
results in fatigue, palpitation, or dyspnea.
ClassIII
Fc III
Comfortable at rest, but less than ordinary activity
causes fatigue, palpitation, or dyspnea.
ClassIV
Fc IV
Symptoms at rest.
Left Heart Failure Signs
 Anxiety,
confusion, restlessness
 Persistent cough
» Pink, frothy sputum
 Tachycardia
 Tachypnea
 Noisy,
labored breathing
» Rales, wheezing (“cardiac asthma”)
 Cyanosis
(late)
 Third heart sound (S3)
Management
Primary
assessment & Focused
Hx
Identify source of problem
» Acute pulmonary edema
» Volume problem
» Pump problem
» Rate problem
Acute Pulmonary Edema
Management
Sit
patient up,
» Do not lay flat
Oxygen
by non-rebreather mask
Consider positive pressure
ventilation
Acute Pulmonary Edema
Management
Consider
intubation if:
» O2 saturation cannot be kept >90%
on 100% O2
» PaO2 cannot be kept >60 torr on
100 % O2
» Patient displays signs of
worsening cerebral hypoxia
» PaCO2 progressively increases
» Patient becoming exhausted
Acute Pulmonary Edema
Management
First
line interventions
» IV / O2 / ECG Monitor
» If BP > 90-100 mm Hg:
 Nitroglycerin
0.4 mg SL
 Morphine 2 – 10 mg slow IV
 furosemide 0.5 – 1.0 mg/kg slow IV
(or twice patient’s single daily dose
up to 120 mg)
» If BP < 90 mm Hg:
 Vasopressors
based on SBP
CHF First Line Drug Therapy
 Nitroglycerin
»
»
»
»
»
»
0.4mg SL q 5 min prn
Systolic BP should be > 90 - 100 mm Hg
Nitrate therapy before IV is started
Reduces preload/afterload
Improves coronary artery perfusion
Caution in RVF
 NTG,
Lasix or MS may worsen hypotension
 Use inotropes if fluid does not improve BP
following NTG administration
CHF First Line Drug Therapy
 Morphine
Sulfate
» 2 mg IV push slowly q 10-15 min
» Peripheral vasodilation leads to
 Decreased
preload
 Decreased afterload
» Decreased venous return leads to
 Decreased
cardiac work
 Decreased O2 demand
» Decreased anxiety
 Decreased
release of catecholamines
» Monitor Ventilations and BP
 Systolic
BP should be > 90 - 100 mm Hg
CHF First Line Drug Therapy
 Furosemide
(Lasix®) -
» 40 mg (0.5 - 1 mg/kg) slow IV
 Patients
already on furosemide may have
tolerance
 Increase dose to 2X daily oral dose
» Direct vasodilation leads to decreased
venous return
» Diuresis leads to decreased intravascular
volume
» May cause hypokalemia, dysrhythmias
 especially
dangerous if patient on digitalis
» May worsen hypotension in RVF
Volume Management
If
rate/rhythm adequate, treat
BP
» Consider fluid challenge of 250cc
LR over 10-15 minutes if relative
or absolute hypovolemia possible,
including RVF and No pulmonary
edema
» Avoid use of vasopressors until
volume deficits corrected or
pulmonary edema presents
Pump Problem
IV
/ O2 / ECG Monitor
SBP <70 mmHg:
» norepinephrine 0.5 – 30 mcg/min IV
inf
SBP
70 – 100 mm Hg & shock
» dopamine 5 – 15 mcg/kg/min IV inf
SBP
> 100 mm Hg w/o shock
» dobutamine 2 – 20 mcg/kg/min IV inf
Dopamine
2
- 20 mcg/kg/min
» Place 200 mg/250cc of D5W
» Begin at 5 mcg/kg/min
» In 2 - 10 mcg/kg/min range,  effects
dominate
» > 20 mcg/kg/min  effects dominate
» Use lowest dose that produces good
perfusion
 May cause tachycardia, ectopy, nausea

DO NOT use until hypovolemia is corrected
Norepinephrine
 0.5
- 30 mcg/min
 Inotropic and vasoconstrictive
properties
 Can be used if systolic BP < 70
 If systolic BP > 70, use dopamine
instead
 DO NOT use until hypovolemia
corrected
CHF Second Line Therapy
Dobutamine
» 2 - 20 mcg/kg/min
» Potent 1 stimulation
 Increases
contractility
 Increases level of cardiac output
» Drug of choice if systolic BP >100
CHF Second Line Therapy
Nitroglycerin
» 10 mcg/min increased by 5-10
mcg/min q 5 min
» Vasodilation
 Decreased
venous return leads to
» Decreased cardiac work
» Decreased O2 demand
 Decreased afterload leads to increased
cardiac output
CHF Third Line Drug Therapy
Bronchodilators
(beta agonists)
» May be useful if wheezing is present
» Mild peripheral vasodilator
» Myocardial and respiratory
stimulant
» May cause arrhythmias in hypoxic
patients or those with coronary
artery disease
HFSA 2010 Practice Guideline
Recommendation
Acute HF—Diagnosis
12.1
The
diagnosis of ADHF should be based primarily
on signs and symptoms.
Strength of
Evidence = C
When
the diagnosis is uncertain, determination of
BNP or NT-proBNP concentration is recommended in
patients being evaluated for dyspnea who have signs
and symptoms compatible with HF. Strength of
Evidence = A
The
natriuretic peptide concentration should not be
interpreted in isolation,
BNP Levels with Different Heart Failure Classes
(NYHA = New York Heart Association)
CHF Class/Stage BNP Levels (pg/mL)
Mild (NYHA Class I)
83-152
Mild to moderate (NYHA Class II) 235-322
Moderate to severe (NYHA ClassIII) 459-590
Severe (NYHA Class IV)
960-1119
BNP<100(not HF)
BNP>400(HF)
NT-proBNP<400(not HF) NT-proBNP>2000(HF)
HFSA 2010 Practice Guideline
Acute HF—IV Vasodilators
Recommendation
12.17
In the absence of symptomatic
hypotension, intravenous
nitroglycerin, nitroprusside or
nesiritide may be considered as an
addition to diuretic therapy for rapid
improvement of congestive
symptoms Strength of Evidence = B
HFSA 2010 Practice Guideline
Acute HF—IV Vasodilators
Recommendation
12.18
Intravenous
vasodilators
(intravenous nitroglycerin or
nitroprusside) and diuretics are
recommended for rapid symptom
relief in patients with acute
pulmonary edema or severe
hypertension.
Strength of Evidence =
C
HFSA 2010 Practice Guideline
Acute HF—Hemodynamic Monitoring
Recommendation
12.22
Invasive hemodynamic monitoring should
be considered in a patient:
Rrefractory to initial therapy
» Volume status and cardiac filling pressures
are unclear
» Significant hypotension (typically SBP < 80
mm Hg)
» Documentation of an adequate hemodynamic
response to the inotropic agent is necessary.
>>
Strength of Evidence = C
Right-sided Heart Failure
Right
ventricle fails as
effective pump
Right ventricle cannot eject
blood returning through vena
cavae
Blood backs up into systemic
circulation
Right Heart Failure Causes
Most Common Cause:
Left sided Heart Failure
Right Heart Failure Causes
Others
» Chronic hypertension
» COPD (cor pulmonale)
» Pulmonary embolism
» Right ventricular infarction
Right Heart Failure
Signs/Symptoms
Tachycardia
Jugular
vein distension
Pedal, pre-tibial, sacral edema
Hepatomegaly
Splenomegaly
Classic Triad of Right Ventricular Failure:
JVD, Hypotension, Clear Lungs
Right Heart Failure
Signs/Symptoms
Anasarca
(generalized edema)
Fluid accumulation in body
cavities
» Ascites
» Pleural effusion
» Pericardial effusion
Heart Failure in Patients with
Reduced Ejection Fraction
HFSA 2010
Recommendations
Evidence-Based Treatment Across the
Continuum of Systolic LVD and HF
Control Volume
Diuretics
Renal Replacement
Therapy*
Improve Clinical Outcomes
Aldosterone
ACEI
-Blocker Antagonist
or ARB
or ARB
CRT 
an ICD*
HDZN/ISDN*
*In selected patients
Treat Residual Symptoms
Digoxin
Compensatory Mechanisms
HFSA 2010 Practice Guideline
ACE Inhibitors
Recommendation
7.1
ACE
inhibitors are recommended for
routine administration to symptomatic and
asymptomatic patients with LVEF ≤ 40%.
Strength of Evidence = A
ACE
inhibitors should be titrated to doses
used in clinical trials, as tolerated during
concomitant uptitration of beta blockers.
Strength of Evidence = C
ACE Inhibitors in Heart Failure:
From Asymptomatic LVD to Severe HF
(Asymptomatic LVD)
20%
29%
death or HF hosp.
death or new HF
(Chronic Heart Failure)
16%
(Severe Heart Failure)
40%
mortality at 6 mos.
31%
mortality at 1 year
27%
mortality at end of
study
mortality
SOLVD Investigators. N Engl J Med 1992;327:685-91
SOLVD Investigators. N Engl J Med 1991;325:293-302
CONSENSUS Study Trial Group. N Engl J Med 1987;316:1429-35
HFSA 2010 Practice Guideline
ACE Inhibitors
Generic
Name
Trade Name
Initial
Daily Dose
Target Dose Mean Dose
in Clinical
Trials
Captopril
Capoten
6.25 mg tid
50 mg tid
122.7 mg/day
Enalapril
Vasotec
2.5 mg bid
10 mg bid
16.6 mg/day
Fosinopril
Monopril
5-10 mg qd
80 mg qd
N/A
Lisinopril
2.5-5 mg qd
20 mg qd
Quinapril
Zestril,
Prinivil
Accupril
5 mg bid
80 mg qd
4.5 mg/day,
33.2 mg/day*
N/A
Ramipril
Altace
1.25-2.5 mg qd
10 mg qd
N/A
Imidapril
Tanatril
2.5 mg qd
10 mg qd
N/A
*No mortality difference between high and low dose groups, but 12% lower risk of
death or hospitalization in high dose group vs. low dose group.
HFSA 2010 Practice Guideline
ARBs
Recommendation
7.3
ARBs
are recommended for routine
administration to symptomatic and
asymptomatic patients with an
LVEF ≤ 40% who are intolerant to ACE
inhibitors for reasons other than
hyperkalemia or renal insufficiency.

A
Strength of Evidence =
HFSA 2010 Practice Guideline
ARBs
Recommendation
7.5
Individual
ARBs may be considered as
initial therapy rather than ACE
inhibitors for patients with the
following conditions:
» HF Post-MI
Strength of Evidence = A
» Chronic HF and reduced LVEF
Strength of Evidence = B
ARBS in Patients Not Taking ACE Inhibitors:
Val-HeFT & CHARM-Alternative
Survival %
ValHeFT
Valsartan
90
CHARM-Alternative
50
CV Death or HF Hosp %

100
80
Placebo
70
60
Placebo
40
30
Candesartan
20
10
p = 0.017
HR 0.77, p = 0.0004
50
0
0
3
6
9
12
15
18
21
24
27
0
9
Months
18
27
Months
Maggioni AP et al. JACC 2002;40:1422-4
Granger CB et al. Lancet 2003;362:772-6
36
HFSA 2010 Practice Guideline
ARBs
Recommendation
7.13 (NEW in 2010)
The
addition of an ARB should be
considered in patients with HF due to
reduced LVEF who have persistent
symptoms or progressive worsening
despite optimized therapy with an ACE
inhibitor and beta blocker.

Strength of Evidence = A
HFSA 2010 Practice Guideline
ARBs
Generic Name
Trade
Name
Initial
Daily Dose
Target
Dose
Mean Dose
in Clinical
Trials
Candesartan
Atacand,
blopress
4-8 mg qd
32 mg qd
24 mg/day
Losartan
Cozaar
12.5-25 mg
qd
150 mg qd
129 mg/day
Olmesartan
Olmetec
5mg qd
40mg qd
Valsartan
Diovan
40 mg bid
160 mg bid 254 mg/day
HFSA 2010 Practice Guideline
Beta Blockers
Recommendation
7.6
Beta-blockers
shown to be effective in
clinical trials of patients with HF are
recommended for patients with an LVEF ≤
40%.
Strength of Evidence = A
% of Patients With Event
COPERNICUS: Death, Hospitalization,
in High Risk Patients
30
HR = 0.67 (CI = 0.47-0.96)
20
Placebo
10
Carvedilol
0
0
2
4
6
Weeks After Randomization
8
Krum H et al. JAMA 2003;289:754-6
Krum et al. JAMA 2003;289
IMPACT-HF Primary End Point:
Patients Receiving Beta Blocker at 60
Days
Improvement
100%
91%
73%
75%
Patients
18%
P <.0001
50%
25%
0%
Carvedilol
Predischarge Initiation
(n=185)
Physician Discretion
Postdischarge Initiation*
(n=178)
Gattis WA et al. JACC 2004;43:1534-41
HFSA 2010 Practice Guideline (7.8)
Pharmacologic Therapy: Beta Blockers
 RECENT
DECOMPENSATION
 Beta blocker therapy is recommended for
patients with a recent decompensation of
HF after optimization of volume status and
successful discontinuation of IV diuretics
and vasoactive agents.
 Whenever possible, beta blocker therapy
should be initiated in the hospital at a low
dose prior to discharge of stable patients.
Strength of
Evidence = B
Adapted from:
HFSA 2010 Practice Guideline
Beta Blockers and ACE Inhibitors
Recommendation
7.7
The
combination of a beta-blocker and
an ACE inhibitor is recommended as
routine therapy for asymptomatic
patients with an LVEF ≤ 40%
» Post MI
» Non Post-MI
Strength of Evidence = B
Strength of Evidence = C
HFSA 2010 Practice Guideline
Beta Blockers
Recommendation
7.10
It
is recommended that beta blockade be
initiated at low doses and uptitrated
gradually, typically:
 At 2-week intervals in patients with reduced
LVEF
 After 3-10 day intervals in patients with
reduced LVEF following newly diagnosed MI.
Strength of Evidence = B
HFSA 2010 Practice Guideline
Beta Blockers
A temporary reduction of dose (generally
by one-half) in this setting may be
considered. Abrupt discontinuation in
patients with symptomatic exacerbation
should be avoided, unless the situation is
life-threatening
Strength of

Evidence = C
» If discontinued or reduced, beta blockers
should be reinstated before the patient is
discharged. In general, doses should be
uptitrated to the previous well-tolerated dose
as soon as safely possible.
HFSA 2010 Practice Guideline
Beta Blockers
Generic
Name
Trade
Name
Initial
Daily Dose
Target
Dose
Mean Dose
in Clinical
Trials
Bisoprolol
Zebeta,
concor
Coreg,
dilatrend
Coreg CR
1.25 mg qd
10 mg qd
8.6 mg/day
3.125 mg bid
25 mg bid
37 mg/day
10 mg qd
80 mg qd
Toprol XL
12.5-25 mg
qd
200 mg qd
Carvedilol
Carvedilol
Metoprolol
succinate
CR/XL
159 mg/day
HFSA 2010 Practice Guideline (7.9)
Pharmacologic Therapy: Beta
Blockers
 CONCOMITANT DISEASE

Beta blocker therapy is recommended in the great
majority of patients with HF and reduced LVEF—even
if there is concomitant diabetes, chronic obstructive
lung disease or peripheral vascular disease.
» Use with caution in patients with:
Diabetes with recurrent hypoglycemia
 Asthma or resting limb ischemia.
» Use with considerable caution in patients with marked
bradycardia (<55 bpm) or marked hypotension (SBP < 80
mmHg).
» Not recommended in patients with asthma with active
bronchospasm.
Strength of Evidence = C

Diabetes and the Use of Beta Blockers for HF: Relative
Risk for Mortality and Hospitalization for Heart Failure
COPERNICUS (carvedilol)1
With diabetes
Without diabetes
MERIT-HF (ER metoprolol succinate)2
With diabetes
Without diabetes
0
0.5
1.0
1.5
2.0
Mohacsi. Circulation. 2001;104(17):abstr 3551.
Hjalmarson. JAMA. 2000;283(10):1295.
HFSA 2010 Practice Guideline (11.8, 15.2)
Pharmacologic Therapy: Beta
Blockers

PRESERVED LVEF

Beta blocker treatment is recommended in patients with
HF and preserved LVEF who have:
» Prior MI
Strength of Evidence = A
» Hypertension
Strength of Evidence = B
» Atrial fib. requiring control of ventricular rate
Strength of Evidence = B

THE ELDERLY

Beta-blocker and ACE inhibitor therapy is recommended
as standard therapy in all elderly patients with HF due to
LV systolic dysfunction.
Strength of Evidence
=B

In the absence of contraindications, these therapies are
also recommended in the very elderly (age > 80 years).
Effect of Beta Blockade on
Outcome in Patients With HF and
Post-MI LVD
Study
US Carvedilol1
Drug
Carvedilol
(dilatrend)
HF
Severity
Target
Dose (mg)
Outcome
mild/
moderate
6.2525 BID
↓48% disease progression
(p= .007)
CIBIS-II2
Bisoprolol
(concor)
moderate/
severe
10 QD
↓34% mortality (p <.0001)
MERIT-HF3
metoprolol
succinate
mild/
moderate
200 QD
↓34% mortality (p =
.0062)
COPERNICU
S4
carvedilol
severe
25 BID
↓35% mortality (p =
.0014)
CAPRICORN5
carvedilol
post-MI
LVD
25 BID
↓23% mortality (p =.031)
HFSA 2010 Practice Guideline
Aldosterone Antagonists
Recommendation
7.14
Administration
of an aldosterone
antagonist is recommended for patients
already receiving standard therapy,
including diuretics, who have:
» NYHA class IV HF (or class III, previously
class IV) from reduced LVEF (≤ 35%)
Strength of Evidence = A
Aldosterone Antagonists in HF
 RALES
Probability of Survival
HF)
(Advanced
EPHESUS (Post-MI)
1.00
1 .0 0
0.90
Eplerenone
0 .9 0
Spironolactone
0.80
Placebo
0 .8 0
0.70
0 .7 0
0.60
Placebo
0 .6 0
0 .5 0
0.50
RR = 0.70
P < 0.001
RR = 0.85
P < 0.008
0.40
0
3
6
9
12 15 18 21 24 27 30 33 36
0 .4 0
0
3
6
9
12 15 18 21 24 27 30 33 36
Months
Pitt B. N Engl J Med 1999;341:709-17
Pitt B. N Engl J Med 2003;348:1309-21
Aldosterone Antagonists in HF
 RALES
Probability of Survival
HF)
(Advanced
EPHESUS (Post-MI)
1.00
1 .0 0
0.90
Eplerenone
0 .9 0
Spironolactone
0.80
Placebo
0 .8 0
0.70
0 .7 0
0.60
Placebo
0 .6 0
0 .5 0
0.50
RR = 0.70
P < 0.001
RR = 0.85
P < 0.008
0.40
0
3
6
9
12 15 18 21 24 27 30 33 36
0 .4 0
0
3
6
9
12 15 18 21 24 27 30 33 36
Months
Pitt B. N Engl J Med 1999;341:709-17
Pitt B. N Engl J Med 2003;348:1309-21
HFSA 2010 Practice Guideline
Aldosterone Antagonists
Recommendation
7.16
Aldosterone
antagonists
are not recommended when:
» creatinine is > 2.5 mg/dL
(or creatinine clearance is < 30 ml/min)
» or serum potassium is > 5.0 mmol/L
» or in conjunction with other potassiumsparing diuretics. Strength of Evidence = A
xHFSA 2010 Practice Guideline
Aldosterone Antagonists
Recommendation
7.17
It
is recommended that serum
potassium concentration be monitored
frequently following initiation or change
in an aldosterone antagonist.
Strength of Evidence = A
Potassium-Sparing Diuretics
Agent
Initial Daily
Dose
Max Total
Daily Dose
Elimination
Duration of
Action
Spironolactone
12.5-25 mg
qd
50 mg
Metabolic
48-72 hrs
Eplerenone
25-50 mg qd
100 mg
Renal,
Metabolic
Amilioride
5 mg qd
Triamterene
50-75 mg bid
20 mg
200 mg
Renal
24 hrs
Metabolic
7-9 hrs
HFSA 2010 Practice Guideline
Hydralazine and Oral Nitrates
Recommendation
7.19
A
combination of hydralazine and isosorbide
dinitrate is recommended as part of standard
therapy in addition to beta-blockers and ACEinhibitors for African Americans with HF and
reduced LVEF:
» NYHA III or IV HF Strength of Evidence = A
» NYHA II HF
Strength of Evidence = B
HFSA 2010 Practice Guideline
Hydralazine and Oral Nitrates
Recommendation
7.20
A
combination of hydralazine and
isosorbide dinitrate may be considered
in non-African American patients with
HF and reduced LVEF who remain
symptomatic despite optimized
standard therapy.

Strength of Evidence = C
HFSA 2010 Practice Guideline
Other Vasodilators
Generic
Name
Trade
Name
Initial
Daily Dose
Target
Dose
Mean Dose
in Clinical
Trials
Fixed dose
hydralazine
/ isosorbide
dinitrate
BiDil
37.5 mg
hydralazine/
20 mg
isosorbide
dinitrate tid
75 mg
hydralazin
e/ 40 mg
isosorbide
dinitrate
tid
142.5 mg
hydralazine
/ 76 mg
isosorbide
dinitrate/da
y
Hydralazine Apresoline
37.5 mg qid
75 mg qid
270 mg/day
Isosorbide
dinitrate
20 mg qid
75 mg qid
270 mg/day
Isordil
A-HeFT All-Cause Mortality
43% Decrease in Mortality
100
Survival %
Fixed Dose ISDN/HDZN
95
Placebo
90
P = 0.01
85
Days
Baseline Visit
0 Since 100
200
300
400
500
600
Taylor AL et al. N Engl J Med 2004;351:2049-57
1 of 2
HFSA 2010 Practice Guideline
Multi-Drug Therapy
Recommendation
7.21 (1 of 2)
Additional pharmacological therapy should be
considered in patients with HF and reduced LVEF
who have persistent symptoms or progressive
worsening despite optimized therapy with an ACE
inhibitor and a beta blocker.
» The choice of specific agent will be influenced by clinical
considerations, including renal function status, chronic
serum potassium concentration, blood pressure, and volume
status.
» The triple combination of an ACE inhibitor, an ARB, and an
aldosterone antagonist is not recommended due to the high
risk of hyperkalemia.
Strength of Evidence = C
2 of 2
HFSA 2010 Practice Guideline
Multi-Drug Therapy cont’d
Recommendation
7.21 (2 of 2)
Addition
of an ARB
Strength of Evidence = A
Addition of an aldosterone antagonist:
» for severe HF
» for moderate HF
» for post-MI HF
Addition
Strength of Evidence = A
Strength of Evidence = C
Strength of Evidence = A
of hydralazine/isosorbide dinitrate:
» for African-Americans
» for others
Strength of Evidence = A
Strength of Evidence = C
HFSA 2010 Practice Guideline (7.23)
Pharmacologic Therapy: Diuretics
 Diuretic
therapy is recommended to restore
and maintain normal volume status in
patients with clinical evidence of fluid
overload, generally manifested by:
» Congestive symptoms
» Signs of elevated filling pressures
Strength of Evidence = A
 Loop
diuretics rather than thiazide-type
diuretics are typically necessary to restore
normal volume status in patients with HF.
Strength of Evidence = B
Loop Diuretics
Agent
Initial Daily
Dose
Max Total
Daily Dose
Elimination:
Renal – Met.
Duration of
Action
Furosemide
20-40mg qd or
bid
600 mg
65%R/35%M
4-6 hrs
Bumetanide
0.5-1.0 mg qd
or bid
10 mg
62%R/38%M
6-8 hrs
Torsemide
10-20 mg qd
200 mg
20%R/80%M
12-16 hrs
Ethacrynic
acid
25-50 mg qd
or bid
200 mg
67%R/33%M
6 hrs
1 of 2
HFSA 2010 Practice Guideline
Diuretics
Recommendation
7.24 (1 of 2)
The initial dose of diuretic may be
increased as necessary to relieve
congestion. Restoration of normal
volume status may require multiple
adjustments over many days and
occasionally weeks in patients with
severe fluid overload evidenced by
massive edema or ascites.
HFSA 2010 Practice Guideline
Diuretics
Recommendation
7.25
Addition of chlorothiazides or metolazone,
once or twice daily, to loop diuretics should be
considered in patients with persistent fluid
retention despite high dose loop diuretic
therapy.
» Volume status and electrolytes must be
monitored closely when multiple diuretics
are utilized.
Strength of Evidence = C
Thiazide Diuretics
Agent
Initial
Daily Dose
Max Total
Daily Dose
Elimination
Duration
of Action
Chlorothiazide
250-500 mg
qd or bid
12.5-25 mg
qd
1000 mg
Renal
6-12 hrs
24-72 hrs
Hydrochlorothiazide
25 mg qd or
bid
200 mg
65% Renal,
10% into Bile,
25% Unknown
Renal
Metolazone
2.5 mg qd
20 mg
12-24 hrs
Idapamide
2.5 mg qd
5 mg
80% Renal,
10% Bile, 10%
?
Metabolic
Chlorthalidone
100 mg
6-12 hrs
36 hrs
?HFSA 2010 Practice Guideline
Diuretics
Recommendation
7.26
Careful
observation for the development
of side effects, including electrolyte
abnormalities, symptomatic hypotension,
renal dysfunction, or worsening renal
function is recommended in patients
treated with diuretics, especially when used
at high doses and in combination.
Patients should undergo routine
laboratory studies and clinical examination
as dictated by their clinical response.

Strength of Evidence = B
HFSA 2010 Practice Guideline
Recommendation
7.28
Diuretics
It
is recommended that patients and caregivers
be given education that will enable them to
demonstrate understanding of the early signs of
fluid retention and the plan for initial therapy.
=C
Strength of Evidence
Selected
patients may be educated to adjust
daily dose of diuretic in response to weight gain
due to fluid overload (typically short-term weight
gain of 2 to 4 pounds).
=C
Strength of Evidence
HFSA 2010 Practice Guideline
Digoxin
Recommendation
7.29
Digoxin
may be considered to improve
symptoms for patients with reduced LVEF (≤
40) who have signs or symptoms of HF while
receiving standard therapy, including ACE
inhibitors and beta blockers:
» NYHA class II-III
» NYHA class IV
Strength of Evidence = A
Strength of Evidence = B
HFSA 2010 Practice Guideline
Digoxin
Recommendation 7.30
It
is recommended that:
» The dose of digoxin, which should be based
on lean body mass, renal function and
concomitant medications, should be 0.125
mg daily in the majority of patients.
» The serum digoxin level should be < 1.0
ng/mL, generally 0.7-0.9 ng/mL

Strength of Evidence = B
HFSA 2010 Practice Guideline
Digoxin
Recommendation
7.31
Digoxin
should be considered for
achieving adequate control of the
ventricular response to atrial fibrillation
in patients with HF.

Strength of Evidence = B
HFSA 2010 Practice Guideline
Digoxin
Recommendation
7.32
High
doses of digoxin (maintenance
dose > 0.25 mg daily) for the purpose of
rate control are not recommended.
Strength of Evidence = C
HFSA 2010 Practice Guideline
Warfarin
Recommendation
7.33
Treatment
with warfarin (goal INR 2.0-3.0)
is recommended for all patients:
» With HF and chronic or documented paroxysmal,
persistent, or long-standing atrial fibrillation
Strength of Evidence = A
» Or a history of systemic or pulmonary emboli,
including stroke or transient ischemic attack,
unless contraindicated.
Strength of Evidence = C
HFSA 2010 Practice Guideline
Warfarin
Recommendation 7.34
It
is recommended that patients with
anterior MI with documented LV
thrombus be treated with warfarin (goal
INR 2.0-3.0) for the initial 3 months postMI, unless contraindicated.
Strength of Evidence = B
Other
patients with ischemic or nonischemic cardiomyopathy and LV
thrombus should be considered for chronic
anticoagulation,
Strength of Evidence = C
HFSA 2010 Practice Guideline
Long-Term Antithrombotic Therapy
Recommendation
7.35
Long-term treatment with an antiplatelet
agent, generally aspirin in doses of 75-81 mg, is
recommended for patients with HF due to
ischemic cardiomyopathy, whether or not they
are receiving ACE inhibitors.
Strength of Evidence = B
Warfarin (goal INR 2.0-3.0) and clopidogrel (75
mg) also have prevented vascular events in postMI patients and may be considered as lternatives
to aspirin.
Strength of Evidence = B
HFSA 2010 Practice Guideline
Aspirin
Recommendation
7.36
Routine
use of aspirin
is not recommended in patients with
HF without atherosclerotic vascular
disease.
Evidence = C
Strength of
xHFSA 2010 Practice Guideline
Anti-arrhythmics
Recommendation
7.37
Anti-arrhythmic
agents, including
amiodarone, are not recommended for
the primary prevention of sudden death
in patients with HF.
Strength of Evidence = A
HFSA 2010 Practice Guideline
Amiodarone
Recommendation
7.38
In
patients with HF and an ICD,
amiodarone may be considered to
reduce the frequency of recurrent
symptomatic arrhythmias causing ICD
shocks.
Strength of Evidence = C
HFSA 2010 Practice Guideline
PUFA
Recommendation
7.41
n-3
polyunsaturated fatty acids
(PUFA) may be considered to reduce
mortality in HF patients with NYHA
class II-IV symptoms and reduced
LVEF.
Strength of Evidence = B
HFSA 2010 Practice Guideline
ICD Placement
Recommendation
9.6
ICD
implantation is recommended for
survivors of cardiac arrest from
ventricular fibrillation or
hemodynamically unstable sustained VT
that is not due to a transient, potentially
reversible cause, such as acute MI.
Strength of Evidence = A
ICD Therapy
CLASS I INDICATIONS:
Ischemic cardiomyopathy with LVEF
< 35%, at least 40 days post MI, NYHA class II OR III.
(Strength of Evidence = A)
2. Ischemic cardiomyopathy with LVEF < 30%, at
least 40 days post MI, NYHA class I. (Strength of
Evidence = A)
3. Non Ischemic cardiomyopathy with LVEF ≤ 35%,
NYHA class II OR III. (Strength of Evidence = B)
1.
MADIT II: Prophylactic ICD in
Ischemic LVD (LVEF 30%)
Probability of Survival
1.0
.9
.8
Defibrillator
.7
Conventional
Therapy
.6
0
0
at
Risk
Defibrillator
Conventional
1
2
3
4
Year
Number
742
490
503
(.91)
329 (.90)
274
(.84)
170 (.78)
110
(.78)
65 (.69)
9
3
Moss AJ et al. N Engl J Med 2002;346:877-83
Moss AJ, et al. N Engl J Med. 2002;346;877-883.
ICD Therapy in the SCD-HeFT Trial:
Mortality by Intention-to-Treat
HR
97.5% Cl
P Value
Amiodarone vs Placebo
1.06
.86-1.30
.53
ICD vs Placebo
.77
.62-.96
.007
.4
Mortality
.3
22%
.2
17%
.1
Amiodarone
ICD Therapy
Placebo
0
0
6
12
18
24
30
36
Months of Follow-Up
42
48
54
60
Bardy GH et al. N Engl J Med 2005;352:225-37
HFSA 2010 Practice Guideline
Biventricular Pacing
Recommendation
Biventricular
for
9.7
pacing therapy is recommended
patients with all of the following:
»
»
»
»
Sinus rhythm
A widened QRS interval (≥120 ms)
Severe LV systolic dysfunction (LVEF < 35%)
Persistent, moderate to severe HF (NYHA III)
despite optimal medical therapy.
Strength of Evidence = A
HFSA 2010 Practice Guideline
Biventricular Pacing
Recommendation
9.8 (NEW in 2010)
Biventricular
pacing therapy may be
considered for patients with AF with a
widened QRS interval (≥ 120 ms) and
severe LV systolic dysfunction (LVEF ≤
35%) who have persistent, moderate to
severe HF (NYHA III) despite optimal
medical therapy.

Strength of Evidence = A
HFSA 2010 Practice Guideline
Biventricular Pacing
Recommendation
9.9
Selected
ambulatory NYHA IV
patients in sinus rhythm with QRS ≥
120 ms and LV systolic dysfunction
may be considered for biventricular
pacing therapy.

Strength of Evidence = B
HFSA 2010 Practice Guideline
Biventricular Pacing
Recommendation
9.10
Biventricular
pacing therapy should
be considered in patients with
reduced LVEF and QRS ≥ 150 ms
who have NYHA I-II HF symptoms.

Strength of Evidence = B
% Event-Free Survival
Effect of CRT Without an ICD on
All-Cause
Mortality:
CARE-HF
100
75
50
risk
CRT
Medical
Therapy
Medical
Therapy
25
HR = 0.64 (95% CI = .48-.85)
p = .0019
0
Number
CRT
at
0
409
404
500
376
365
351
321
Days
213
192
1,000
89
71
1,500
8
5
Cleland JG et al. N Engl J Med 2005;352:1539-49
Percentage of Patients Free of Death from Any Cause or
Unplanned Hospitalization for Major Cardiovascular Event
Cardiac
Resynchronizatio
n Therapy
Prolongs Survival
in Patients With
Heart Failure
(The CARE-HF
Trial)
Cleland JG et al. N Engl J Med. 2005:352;1539.
Percentage of Patients Free of Death from Any Cause
Left Ventricular Assist
Devices (LVAD)
The Jarvik 2000
The Jarvik-7
The World's First Artificial Heart
Transcutaneous Ventricular
Assist Device
Implantable Ventricular Assist
Device
Ventricular Assist Device
in the market
Thoratec CentriMag® Thoratec PVAD™
HeartMate II®
Thoratec IVAD™
Arrow LionHeart
HeartMate® XVE
DeBakey LVAD
Surgeries for heart failure
Coronary Revascularization
Valvular Surgery
Left Ventricular Reconstructive
Surgery (Dor Procedure)
Cardiac
Transplant
On December 3rd 1967
At Groote Schuur Hospital
Mr. Louis Washkansky lived for 18 days
1967 Cape Town / Dr.Barnard
Thank you
very much !!!
Figure 11.3. Diagnostic Algorithm
for HF with Preserved LVEF
HF with
Preserved LVEF
Dilated LV
Valvular disease
AR, MR
Non-dilated LV
No valvular dis.
High output HF
Increased
thickness
Normal or
increased QRS
Hypertrophic dis.
No aortic
valve disease
No hypertensive
history of PE
HCM, Fabry dis.
Normal
Thickness
Low QRS voltage
Infiltrative
myopathy
Aortic valve dis.
Aortic stenosis
Hypertensive
history of PE
Hypertensive-HCM
Some patients with RV
dysfunction have LV
dysfunction due to
ventricular interaction.
Right vent.
dysfunction
No mitral
obstruction
Pulmonary
hypertension
Pericardial dis.
Tamponade
Constriction
Isolated predominant RVMI
No pericardial
disease
Inducible ischemia
Intermittent/active
ischemia
Mitral obstruction
MS, atrial myxoma
No inducible ischemia, fibrotic, collagenVascular, RCM, cardinoid, diabetes,
Radiation or chemotherapy induced
heart disease, infiltrative disease, comorbid conditions, reconsider diagnosis
of HF
HFSA 2010 Practice Guideline (9.1, 9.4)
Device Therapy:
Prophylactic ICD Placement
Prophylactic
ICD placement should be considered in
patients with an LVEF ≤35% and mild to moderate HF
symptoms:
»
»
Ischemic etiology
Non-ischemic etiology
Strength of Evidence = A
Strength of Evidence = B
In
patients who are undergoing implantation of a
biventricular pacing device, use of a device that provides
defibrillation should be considered.
Strength of
Evidence = B
Decisions
should be made in light of functional status
and prognosis based on severity of underlying HF and
comorbid conditions, ideally after 3-6 mos. of optimal
medical therapy.
Strength of
Evidence = C
Adapted from:
Management
Monitor
ECG
» Hypoxia, increased heart wall
tension leads to dysrhythmias
IV
NS TKO via microdrip or
lock
» Limit Fluids
» If RVF only, fluid challenges to 
preload
Volume Problem
IV/O2/ECG
Monitor
Fluid challenge until rales or if
evidence of anterior wall AMI
Vasopressors based on SBP
Management
IV
TKO with microdrip set or lock
» Limit fluids unless suspect RVF
Correct
rhythm
major disorders of rate,
» Increase rate in bradycardias
» Terminate tachycardias with
cardioversion
» Suppress frequent ectopic beats
BP Treatment Review
If
rate, rhythm, volume
adequate, treat BP with
vasopressors:
» Norepinephrine, or
» Dopamine
CHF Management
 What
if the BP is too low for the first
and second line drug therapies?
» BP < 70 mm Hg
 norepinephrine,
0.5 - 30 mcg/min IV infusion
» BP > 70 but < 100 mm Hg
 dopamine,
 After
5 - 15 mcg/kg/min IV infusion
BP improves, treat pulmonary
edema with first and second line
therapies
CHF Management
 Long
Term Management usually includes
» Fluid minimization
 Diuretics
(+ Potassium if non-potassium sparing)
 Diet restrictions
» Increase contractility
 Digitalis
» Blood pressure control
 ACE
Inhibitors
» Coronary artery perfusion
 Nitroglycerin
HFSA 2010 Practice Guideline (12.3, Table 12.3)

Acute Decompensated Heart Failure
(ADHF)—Treatment Goals for Hospitalized
Improve symptoms,Patients
especially congestion and low-
output symptoms
 Optimize volume status
 Identify etiology
 Identify precipitating factors
 Optimize chronic oral therapy; minimize side
effects
 Identify who might benefit from revascularization
 Education patients concerning medication and HF
self-assessment
Strength of Evidence = C
 Consider enrollment in a disease management
program
HFSA 2010 Practice Guideline (12.5-12.20)
Overview of Treatment Options for Patients
with Acute Decompensated HF
» Fluid and sodium restriction
» Diuretics, especially loop diuretics
» Ultrafiltration/renal replacement
therapy (in selected patients only)
» Parenteral vasodilators *
(nitroglycerin, nitroprusside,
nesiritide)
» Inotropes * (milrinone or
dobutamine)
Goals of Management
Improve
oxygenation, ventilation
Decrease venous return to heart
Decrease cardiac work, O2
demand
Improve cardiac output by
» Reducing afterload
» Increasing myocardial contractility
HFSA 2010 Practice Guideline
ACE Inhibitors
Recommendation
7.2
In patients who cannot tolerate ACE
inhibitors due to cough, ARBs are
recommended. Strength of Evidence = A
» The combination of hydralazine and an
oral nitrate may be considered in such
patients not tolerating ARB therapy.
Strength of Evidence = C

HFSA 2010 Practice Guideline (7.14-7.15)
Pharmacologic Therapy:
Aldosterone Antagonists
An
aldosterone antagonist is recommended
for patients on standard therapy, including
diuretics, who have:
»
NYHA class IV HF (or class III, previously class
IV) HF from reduced LVEF (≤ 35%)
One
should be considered in patients post-MI
with clinical HF or diabetes and an LVEF <
40% who are on standard therapy, including an
ACE inhibitor (or ARB) and a beta blocker.
Strength of Evidence = A
Adapted from:
HFSA 2010 Practice Guideline
Recommendation
Amiodarone
7.39
It
is recommended that when amiodarone therapy
is initiated, the potential for interactions with
other drugs be reviewed.
The maintenance doses of digoxin, warfarin, and
some statins should be reduced when amiodarone
is initiated and then carefully monitored.
Adjustment in doses of these drugs and
laboratory assessment of drug activity or serum
concentration after initiation of amiodarone is
recommended.
Strength of Evidence = A