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HEART FAILURE
Adapted From:
American Heart Association
Chronic Congestive Heart Failure
Committee on Post Graduate Education,
Council on Clinical Cardiology,
American Heart Association
Developed in collaboration with the
Sociedad Española de Cardiología
Prepared by:
Ann F. Bolger, MD
José López-Sendón, MD
The content of these slides is current as of March 2003
Future revisions will be posted on the
American Heart Association website (www.americanheart.org).
Chronic Congestive Heart Failure
Definition of Heart Failure
Clinical syndrome that can result from any
structural or functional cardiac disorder that
impairs the ability of the ventricle to fill with
or eject blood
Chronic Congestive Heart Failure
Epidemiology
• 5,000,000 patients
• 6,500,000 hospital days / year
• 300,000 deaths / year
• 10% of people > 65 years
• 5.4% of healthcare budget ($28 billion)
• Incidence x 2 in last ten years
Gottdiener J et al. JACC 2000;35:1628
Haldeman GA et al. Am Heart J 1999;137:352
Kannel WB et al. Am Heart J 1991;121:951
O’Connell JB et al. J Heart Lung Transplant 1993;13:S107
Chronic Congestive Heart Failure
Suspect Heart Failure
Assess presence of CARDIAC DISEASE
by PE, EKG, CXR, or BNP
NORMAL
No Heart Failure
ABNORMAL
Assess LV FUNCTION
by Echocardiogram, Nuclear
angiography, or MRI if available
ABNORMAL
Heart Failure
NORMAL
No Heart Failure
Chronic Congestive Heart Failure
Risk Factors
Gottdiener J et al. The Cardiovascular Health Study JACC 2000;35:1628
Chronic Congestive Heart Failure
Direct Causes
1- Myocardial Abnormalities (CHD)
2- Hemodynamic Overload
3- Ventricular Filling Abnormalities
4- Ventricular Dyssynergy
5- Changes in Cardiac Rhythm
Chronic Congestive Heart Failure
Aggravating Factors
• Medications
• New Heart Disease
• Myocardial Ischemia
• Pregnancy
• Endocarditis
• Arrhythmias (AF)
• Obesity
• Infections
• Hypertension
• Thromboembolism
• Physical Activity
• Hyper/hypothyroidism • Dietary Excess
Chronic Congestive Heart Failure
Clinical Manifestations
• Dyspnea: First on exertion, then with
progressively less strenuous activity
• Orthopnea: Increased venous return in the
recumbent position
• PND: multiple factors
• Nocturnal Angina: Increased cardiac workload, 2º
to increased venous return
• Cheyne Stokes Respiration: Alternating phases of
apnea and hyperventilation
• Fatigue: low cardiac output
• Peripheral Edema
Chronic Congestive Heart Failure
Physical Exam Findings
Left Sided Failure
•
•
•
•
Pulmonary Rales
Tachypnea
S3 Gallop
Cardiac Murmurs (AS,
AR, MR)
• Paradoxical Splitting
of S2
Right Sided Failure
• Jugular Venous
Distention
• Peripheral Edema
• Peripheral/ Perioral
cyanosis
• Hepatomegaly
• Ascites
• Hepatojugular Reflux
Chronic Congestive Heart Failure
Assessment of JVD
Shasham, Fadi, and Judith Mitchell, M.D. “Essentials of the Diagnosis of Heart Failure.” American Family
Physician, March, 2001.
Chronic Congestive Heart Failure
CXR Findings
• Cardiomegaly
(Cardiothoracic ratio
>0.5)
• Large Hila with
indistinct margins
• Prominence of
superior pulmonary
veins
• Fluid in intralobar
fissures
• Kerley B lines
• Alveolar edema
• Blunting of Angles
Chronic Congestive Heart Failure
Stage A
HF Risk Factors
No Heart Disease
No Symptoms
Stage B
Asymptomatic
Heart Disease
Stages in the
Evolution
of Heart Failure
Stage C
Prior or Current
HF Symptoms
Definitions
Stage D
Refractory
HF
Chronic Congestive Heart Failure
Stage A
HTN, DM, CAD,
Obesity, Metabolic
Syndrome
Stage B
MI, LV Dysfunction,
Valvular Disease
Stages in the
Evolution
of Heart Failure
Stage C
Dyspnea, Fatigue,
Exercise Tolerance
Clinical
Characteristics
Stage D
Symptoms at rest
despite max. therapy
Chronic Congestive Heart Failure
Stage A
Risk Factor Reduction,
ACE-I / ARB in DM &
Vascular DZ
Stage B
ACE-I / ARB, BBlockers
Stages in the
Evolution
of Heart Failure
Stage C
Pharmacologic
Therapy, Devices
Treatment
Stage D
Mechanical Devices,
Heart Transplant
Chronic Congestive Heart Failure
New York Heart Association Classification
Chronic Congestive Heart Failure
Goals of Initial / Ongoing Evaluation
• Identify Heart Disease
• Assess Functional Capacity (NYHA, 6 min walk)
• Assess Volume Status (edema, crackles, JVD,
hepatomegaly, body weight)
• Testing:
Initial: CBC, U/A, CMP, HbA1C, FLP, CXR, EKG, TSH, Echo
Periodic: electrolytes, RFP, Echocardiogram
• Assess Prognosis
Chronic Congestive Heart Failure
% Cardiac Mortality
Prognosis
50
<30
Post MI
n=196
40
30
31-35
20
36-45
10
46-53
0
20
30
40
50
LVEF
Brodie B. et al, Am J Cardiol 1992;69:1113
54-60
>60
60
70
80
Chronic Congestive Heart Failure
Treatment Objectives
Survival
Morbidity
Exercise Capacity
Quality of Life
Neurohormonal Changes
Progression of CHF
Symptoms
Chronic Congestive Heart Failure
Treatment Modalities
Selected Patients
All
• Prevention, Control of Risk Factors
• Lifestyle
• Treat Cause / Aggravating Factors
• Pharmacologic Therapy
• Personal Care / Healthcare Team
• Revascularization for Ischemic Causes
• ICD
• Ventricular Resyncronization
• Ventricular Assist Devices
• Heart Transplant
• Artificial Heart
• Neoangiogenesis, Gene Therapy, Etc.
Chronic Congestive Heart Failure
Pharmacologic Therapy
• Diuretics
• ACE Inhibitors
• Beta Blockers
• Digitalis
• Spironolactone
• Others
Chronic Congestive Heart Failure
Diuretics
• Essential to Control Symptoms
Secondary to Fluid Retention
• Prevent Decompensation
• Loops Increase Sodium Excretion up
to 20 - 25%
• Thiazides Increase Sodium Excretion
by 5 – 10%
Chronic Congestive Heart Failure
Cortex
Diuretics
Thiazides
Inhibit active exchange of Cl-Na
in the cortical diluting segment of the
ascending loop of Henle
K-sparing
Medulla
Inhibit reabsorption of Na in the
distal convoluted and collecting tubule
Loop
Loop diuretics
of
Inhibit exchange of Cl-Na-K in
the thick segment of the ascending
loop of Henle
Henle
Collecting
Tubule
Chronic Congestive Heart Failure
Diuretics: Indications
1.Symptomatic HF, with Fluid Retention
• Edema
• Dyspnea
• Lung Crackles
• Jugular Distension
• Hepatomegaly
• Pulmonary edema (Xray)
Chronic Congestive Heart Failure
Loop Diuretics / Thiazides: Practical Use
• Start with variable dose. Titrate to achieve
dry weight.
• Monitor serum K+ at “frequent intervals.”
• Reduce dose when fluid retention is controlled.
• Teach the patient when, how to adjust dose.
• Combine with ACE-I and B-Blocker
Chronic Congestive Heart Failure
Loop diuretics: Dose (mg)
Initial
Maximum
Bumetanide
0.5 to 1.0 / 12-24h
10 / day
Furosemide
20 to 40 / 12-24h
400 / day
Torsemide
10 to 20 / 12-24h
200 / day
Chronic Congestive Heart Failure
Loop Diuretics / Thiazides: Adverse Effects
•
K+, Mg+ (15 - 60%)
•
Na+
• Stimulation of Neurohormonal Activity
• Hyperuricemia (15 - 40%)
• Hypotension, Ototoxicity, Gastrointestinal Sx,
Metabolic Alkalosis
Sharpe N. Heart failure. Martin Dunitz 2000;43
Kubo SH , et al. Am J Cardiol 1987;60:1322
MRFIT, JAMA 1982;248:1465
Pool Wilson. Heart failure. Churchill Livinston 1997;635
Chronic Congestive Heart Failure
Diuretics: Resistance
• Neurohormonal Activation
• Rebound Na+ uptake after Volume Loss
• Hypertrophy of Distal Nephron
• Reduced Tubular Secretion (renal failure,
NSAIDs)
• Decreased Renal Perfusion (low output)
• Altered Absortion
• Noncompliance
Brater NEJM 1998;339:387
Kramer et al. Am J Med 1999;106:90
Chronic Congestive Heart Failure
Managing Resistance to Diuretics
• Restrict Na+/H2O intake
• Increase Dose
• Combine: furosemide + thiazide / spiro / metolazone
• Dopamine (increase cardiac output)
• Reduce Dose of ACE-I
• Ultrafiltration
Motwani et al Circulation 1992;86:439
Chronic Congestive Heart Failure
ACE-I: Mechanism of Action
VASOCONSTRICTION
ALDOSTERONE
VASOPRESSIN
SYMPATHETIC
VASODILATATION
PROSTAGLANDINS
Kininogen
tPA
Kallikrein
Angiotensinogen
RENIN
Angiotensin I
A.C.E.
ANGIOTENSIN II
Inhibitor
BRADYKININ
Kininase II
Inactive Fragments
Chronic Congestive Heart Failure
ACE-I: Clinical Effects
• Improve Symptoms
• Reduce Remodeling / Progression
• Reduce Hospitalization
• Improve Survival
Chronic Congestive Heart Failure
Mortality Reduction with ACE-I
Study
ACE-I
Clinical Seting
CONSENSUS
Enalapril
CHF
SOLVD treatment Enalapril
CHF
AIRE
Ramipril
CHF
Vheft-II
Enalapril
CHF
TRACE
Trandolapril
CHF / LVD
SAVE
Captopril
LVD
SMILE
Zofenopril
High Risk
HOPE
Ramipril
High Risk
Chronic Congestive Heart Failure
CONSENSUS
Probability of Death
0.8
0.7
Placebo
0.6
p< 0.001
0.5
0.4
0.3
Enalapril
0.2
0.1
0
0
1
2
3
4
5
6
7
Months
N Engl J Med 1987;316:1429
8
9
10 11 12
Chronic Congestive Heart Failure
SOLVD (Treatment)
NYHA II-III
EF < 35%
% Mortality
50
p = 0.0036
Placebo
n=1284
40
30
Enalapril
n=1285
20
10
0
0
6
12
18
24
30
Months
N Engl J M 1991;325:293
36
42
48
Chronic Congestive Heart Failure
SAVE
30
Placebo
3 - 16 days
post AMI
EF < 40%
Captopril
12.5 - 150 mg/day
n=1116
% Mortality
Asymptomatic
Ventricular
Dysfunction
Post MI
20
Captopril
n=1115
10
² -19%
p=0.019
0
0
N Engl J Med 1992;327:669
1
2
Years
3
4
Chronic Congestive Heart Failure
AIRE
Placebo
HF
S/P
AMI
% Mortality
30
20
Ramipril
10
p = 0.002
0
0
6
12
18
Months
Lancet 1993;342:821
24
30
Chronic Congestive Heart Failure
ACE-I: Indications
• Symptomatic
Heart Failure
• Asymptomatic
Ventricular
Dysfunction
- LVEF < 40%
• Selected High
Risk Subgroups
Chronic Congestive Heart Failure
ACE-I: Practical Use
• Start with very low dose
• Increase dose if well tolerated
• Renal function & serum K+ after 1-2 wks
• Avoid fluid retention / hypovolemia (diuretic use)
• Dose NOT determined by symptoms
• Combine to overcome “resistance”
Chronic Congestive Heart Failure
ACE-I: Dose (mg)
Initial
Maximum
Captopril 6.25 / 8h
50 / 8h
Enalapril
10 to 20 / 12h
2.5 / 12 h
Fosinopril 5 to 10 / day
40 / day
Lisinopril 2.5 to 5.0 / day
20 to 40 / day
Quinapril 10 / 12 h
40 / 12 h
Ramipril
10 / day
1.25 to 2.5 / day
Chronic Congestive Heart Failure
ACE-I: Adverse Effects
• Hypotension (1st dose effect)
• Worsening Renal Function
• Hyperkalemia
• Cough
• Angioedema
Chronic Congestive Heart Failure
ACE-I: Contraindications
• Intolerance (angioedema, anuric renal failure)
• Bilateral Renal Artery Stenosis
• Pregnancy
• Renal Insufficiency (creatinine > 2 mg/dL)
• Hyperkalemia (> 5.5 mmol/l)
• Severe Hypotension
Chronic Congestive Heart Failure
Angiotensin II Receptor Blockers (ARB)
RENIN
Angiotensinogen
Other pathways
AT1
Receptor
Blockers
AT1
Vasoconstriction
Angiotensin I
ACE
ANGIOTENSIN II
RECEPTORS
Proliferative
Action
AT2
Vasodilatation
Antiproliferative
Action
Chronic Congestive Heart Failure
Angiotensin II Receptor Blockers (ARB)
• For Patients who can not take ACE-I
• “Reasonable Alternative” to ACE-I
• Similar in Benefit to ACE-I
– CHARM
• Less Studied than ACE-I
• Combined with ACE-I may Decrease
Morbidity and Mortality???
Chronic Congestive Heart Failure
ARB: Indications
Stage A
B
C
Chronic Congestive Heart Failure
ARB: Dose (mg)
Candesartan
Losartan
Valsartan
Initial
4–8/d
25 – 50 / d
20 – 40 BID
Target
32 / d
50 – 100 / d
160 BID
Chronic Congestive Heart Failure
ß-Blockers: Mechanism of action
• Density of ß1 Receptors
• Inhibit Cardiotoxicity of Catecholamines
• Neurohormonal Activation
• HR
• Antiischemic
• Antihypertensive
• Antiarrhythmic
• Antioxidant, Antiproliferative
Chronic Congestive Heart Failure
ß-Blockers: Clinical Effects
• Improve Symptoms (only long term)
• Reduce Remodelling / Progression
• Reduce Hospitalization
• Reduce Sudden Death
• Improve Survival
Chronic Congestive Heart Failure
US Carvedilol HF
NYHA
I-II
% Survival
1.0
Carvedilol
(n=696)
0.9
p<0.001
0.8
0.7
Placebo
(n=398)
Risk Reduction = 65%
0.6
0
50
100 150 200 250 300 350 400
Days
NEJM 1996; 334: 1349-55
Chronic Congestive Heart Failure
CIBIS-II
1
Bisoprolol
NYHA
III-IV
Survival
0.9
11.8%
0.8
P< 0.00005
Placebo
0.7
17.3%
0.6
0.5
0
Lancet 1999;353:9
200
400
Days
600
800
Chronic Congestive Heart Failure
MERIT-HF
Placebo
15
NYHA
II-IV
% Mortality
p=0.0062
Metoprolol
10
5
Risk Reduction 34%
0
0
3
6
9
12
Months
Lancet 1999; 353: 2001
15
18
21
Chronic Congestive Heart Failure
COPERNICUS
100
90
NYHA
III-IV
%
Survival
80
NEJM 2001;344:1651
Carvedilol
70
p=0.00014
60
Placebo
Risk Reduction 34%
50
0
4
8
12
16
Months
20
24
28
Chronic Congestive Heart Failure
CAPRICORN
1
HR 0.77 (0.60 - 0.98) p<0.031
HF
Post
AMI
Survival
0.95
0.9
Carvedilol
116 / 975 (12%)
0.85
0.8
Placebo
0.75
151 / 984 (15%)
0.7
0
0.5
1
1.5
Years
Lancet 2001;357:1385
2
2.5
Chronic Congestive Heart Failure
ß-Blockers: Indications
• Symptomatic
Heart Failure
• Asymptomatic
Ventricular
Dysfunction
- LVEF < 35%
• After AMI
Stage A
B
C
Chronic Congestive Heart Failure
ß-Blockers: When to Start
• Patient Stable
• No physical evidence of fluid retention
• No need for IV inotropic drugs
• Start ACE-I / Diuretic First
• No Contraindications
• In Hospital or not
Chronic Congestive Heart Failure
ß-Blockers: Dose (mg)
Initial
Target
Bisoprolol
1.25 / 24h
10 / 24h
Carvedilol
3.125 / 12h
25 / 12h
Metoprolol tartrate
6.25 / 12h
75 / 12h
• Start Low, Increase Slowly
• Increase the dose every 2 - 4 weeks
Chronic Congestive Heart Failure
ß-Blockers: Adverse Effects
• Hypotension
• Fluid Retention / Worsening Heart Failure
• Fatigue
• Bradycardia / Heart Block
• Review Treatment (+/-diuretics, other drugs)
• Reduce Dose
• Consider Cardiac Pacing
• Discontinue Beta Blocker only in Severe Cases
Chronic Congestive Heart Failure
ß-Blockers: Contraindications
• Asthma (reactive airway disease)
• AV block (unless pacemaker)
• Symptomatic Hypotension / Bradycardia
• Diabetes is NOT a contraindication
Chronic Congestive Heart Failure
Digitalis: Mechanism of Action
Blocks Na+ / K+ ATPase => Ca+ +
• Inotropic effect
• Natriuresis
• Neurohormonal control
-
Plasma Noradrenaline
Peripheral Nervous System Activity
RAAS Activity
- Vagal Tone
- Normalizes Arterial Baroreceptors
NEJM 1988;318:358
Chronic Congestive Heart Failure
Digitalis
Na-K ATPase
Na+
K+
K+ Na+
Na-Ca Exchange
Na+
Myofilaments
Ca++
Ca++
CONTRACTILITY
Chronic Congestive Heart Failure
Digitalis: Clinical Effects
• Improve Symptoms
• Modest Reduction in Hospitalization
• Does Not Improve Survival
Chronic Congestive Heart Failure
DIG
50
NYHA
II-III
% Mortality
40
30
Placebo
20
n=3403
10
p = 0.8
Digoxin
n=3397
0
0
N Engl J Med 1997;336:525
12
24
Months
36
48
Chronic Congestive Heart Failure
Digitalis: Indications
• When no adequate response to
ACE-I + diuretics + beta-blockers
• In combination with ACE-I + diuretics
if persisting symptoms
• AFib, to slow AV conduction
Dose 0.125 to 0.250 mg / day
Chronic Congestive Heart Failure
Digitalis: Contraindications
• Digoxin toxicity
• Advanced A-V block without pacemaker
• Bradycardia or sick sinus without PM
• PVC’s and VT
• Marked hypokalemia
• WPW with atrial fibrillation
Chronic Congestive Heart Failure
Aldosterone Inhibitors
Spironolactone
ALDOSTERONE
-
Competitive antagonist of the
aldosterone receptor
(myocardium, arterial walls, kidney)
• Retention Na+
• Retention H2O
• Excretion
K+
• Excretion Mg2+
• Collagen
Edema
deposition
Fibrosis
Arrhythmias
- myocardium
- vessels
Chronic Congestive Heart Failure
RALES
1.0
Annual Mortality
Aldactone 18%; Placebo 23%
NYHA
III-IV
Survival
0.9
0.8
Aldactone
0.7
0.6
p < 0.0001
0.5
Placebo
months
NEJM 1999;341:709
0
6
12
18
24
30
36
Chronic Congestive Heart Failure
Spironolactone: Indications
• LV Dysfunction Early After MI
• Moderately Severe or Severe HF with
Recent Decompensation
• Hypokalemia
Chronic Congestive Heart Failure
Spironolactone: Practical Use
• Do not use if hyperkalemia, renal insuf.
• Monitor serum K+ at “frequent intervals”
• Start ACE-I first
• Start with 12.5 - 25 mg / 24h
• If K+ >5.5 mmol/L, reduce to 25 mg / 48h
• If K+ is low or stable consider 50 mg / day
Chronic Congestive Heart Failure
NITRATES
HEMODYNAMIC EFFECTS
1- VENOUS VASODILATATION
Preload
Pulmonary congestion
Ventricular size
Vent. Wall stress
MVO2
2- Coronary vasodilatation
Myocardial perfusion
3- Arterial vasodilatation
Afterload
4- Others
• Cardiac output
• Blood pressure
Chronic Congestive Heart Failure
VHefT-1 (Nitrates)
0.7
Placebo (273)
0.6 Prazosin (183)
Hz + ISDN (186)
0.5
Probability
of
Death
0.4
0.3
0.2
0.1
0
0
N Engl J Med 1986;314:1547
6
12
18
24
Months
30
36
42
Chronic Congestive Heart Failure
V-HeFT II (Nitrate + Hydralazine)
0.75
n = 804
HZ +
0,54ISDN
Probability
of
Death
0.47
0.50
p = 0.016
0,48
0.36
0.25
0.42
0.31
Enalapril
0.25
0.13
0.18
0.09
p = 0.08
0
0
N Engl J Med 1991; 325:303
12
24
36
Months
48
60
Chronic Congestive Heart Failure
Nitrates: Clinical Use
• CHF with myocardial ischemia
• Orthopnea and paroxysmal nocturnal dyspnea
• In acute CHF and pulmonary edema: NTG sl / iv
• Nitrates + Hydralazine in intolerance
to ACE-I (hypotension, renal insufficiency)
Chronic Congestive Heart Failure
Positive Inotropes
• Digitalis
• Sympathomimetics
• Catecholamines
• B-adrenergic agonists
• Phosphodiesterase inhibitors
• Amrinone, Milrinone, Enoximone
• Calcium sensitizers
• Levosimendan, Pimobendan
Chronic Congestive Heart Failure
Positive Inotropic Therapy
•May increase mortality
Exception: Digoxin, Levosimendan
•Use only in refractory CHF
•NOT for use as chronic therapy
Chronic Congestive Heart Failure
Drugs to Avoid (may increase symptoms, mortality)
• Inotropes, long term / intermittent
• Antiarrhythmics (except amiodarone)
• Calcium Channel Blockers
• Non-steroidal antiinflammatory drugs (NSAIDS)
• Tricyclic antidepressants
• Corticosteroids
• Lithium
Chronic Congestive Heart Failure
Refractory End-Stage HF
• Review etiology, treatment & aggrav. factors
• Control fluid retention
• Resistance to diuretics
• Ultrafiltration ?
• IV inotropics / vasodilators during
decompensation
• Consider resynchronization
• Consider mechanical assist devices
• Consider heart transplantation
Chronic Congestive Heart Failure
Heart Transplant: Indications
• Refractory cardiogenic shock
• Documented dependence on IV inotropic support
to maintain adequate organ perfusion
• Peak VO2 < 10 ml / kg / min
• Severe symptoms of ischemia not amenable to
revascularization
• Recurrent symptomatic ventricular arrhythmias
refractory to all therapeutic modalities
Contraindications: age, severe comorbidity
Chronic Congestive Heart Failure
Supraventricular Arrhythmias
• Risk of embolization (AF)
• Anticoagulation in AF
• Systolic & diastolic dysfunction
• Digoxin, beta blockers
• Amiodarone if b-blocker ineffective/ contraind.
Chronic Congestive Heart Failure
Ventricular Arrhythmias / Sudden Death
• Antiarrhythmics ineffective (may increase mortality)
Amiodarone does not improve survival
• -blockers reduce all cause mortality and SD
• Control ischemia
• Control electrolyte disturbances
• ICD (Implantable Cardiac Defibrillator)
• In secondary prevention of sudden death
• In sustained, hemodynamic destabilizing VT
• In LVEF < 30% and mild - moderate HF symptoms
Chronic Congestive Heart Failure
Diastolic Heart Failure
• Incorrect diagnosis of HF
• Inaccurate measurement of LVEF
• Primary valvular disease
• Restrictive (infiltrative) cardiomyopathies (Amyloidosis…)
• Pericardial constriction
• Episodic or reversible LV systolic dysfunction
• Severe hypertension, ischemia
• High output states: Anemia, thyrotoxicosis, etc
• Chronic pulmonary disease with right HF
• Pulmonary hypertension
• Atrial myxoma
• LV Hypertrophy
• Diastolic dysfunction of uncertain origin
Chronic Congestive Heart Failure
Diastolic Heart Failure
• Treat as HF with low LVEF
• Control:
• Hypertension
• Tachycardia
• Fluid Retention
• Myocardial Ischemia
• Ongoing Research
Chronic Congestive Heart Failure
Treatment Summary
Symptoms
Morbidity
Mortality
Increase Dose No effect
of ACEI
↓ 10-15%
No effect
Add ARB
↓
↓ 10-15%
No effect
Add ßblocker
Add
Aldactone
↓
↓ 20-35%
↓ 35%+
↓
↓ 20%
↓ 16-25%
Add ISDN+
Hydralazine
↓
↓ 30%
↓ 40%
AHA Scientific Sessions, 2004 (Lachel et al)
Chronic Congestive Heart Failure