Presentaci

1

HEART FAILURE Adapted From American Heart
Association
2
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).
3
Definition of Heart Failure
4
Epidemiology 5,000,000 patients 6,500,000
hospital days / year 300,000 deaths / year
10 of people gt 65 years 5.4 of healthcare
budget (28 billion) Incidence x 2 in last ten
years
Gottdiener J et al. JACC 2000351628 Haldeman GA
et al. Am Heart J 1999137352 Kannel WB et al.
Am Heart J 1991121951 OConnell JB et al. J
Heart Lung Transplant 199313S107
5
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
NORMAL No Heart Failure
ABNORMAL
Heart Failure
6
Risk Factors
Gottdiener J et al. The Cardiovascular Health
Study JACC 2000351628
7
Direct Causes
1- Myocardial Abnormalities (CHD)2- Hemodynamic
Overload3- Ventricular Filling
Abnormalities4- Ventricular Dyssynergy5-
Changes in Cardiac Rhythm
8
Aggravating Factors

• Medications
• New Heart Disease
• Myocardial Ischemia

• Endocarditis
• Obesity
• Hypertension
• Physical Activity
• Dietary Excess

• Pregnancy
• Arrhythmias (AF)
• Infections
• Thromboembolism
• Hyper/hypothyroidism

9
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

10
Physical Exam Findings

• Right Sided Failure
• Jugular Venous Distention
• Peripheral Edema
• Peripheral/ Perioral cyanosis
• Hepatomegaly
• Ascites
• Hepatojugular Reflux

• Left Sided Failure
• Pulmonary Rales
• Tachypnea
• S3 Gallop
• Cardiac Murmurs (AS, AR, MR)
• Paradoxical Splitting of S2

11
Assessment of JVD
Shasham, Fadi, and Judith Mitchell, M.D.
Essentials of the Diagnosis of Heart Failure.
American Family Physician, March, 2001.
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CXR Findings

• Cardiomegaly (Cardiothoracic ratio gt0.5)
• Large Hila with indistinct margins
• Prominence of superior pulmonary veins
• Fluid in intralobar fissures
• Kerley B lines
• Alveolar edema
• Blunting of Angles

13
Stage A HF Risk Factors No Heart Disease No
Symptoms
Stages in the Evolution of Heart Failure
Stage B Asymptomatic Heart Disease
Stage C Prior or Current HF Symptoms
Definitions
Stage D Refractory HF symptoms
14
Stage A HTN, DM, CAD, Obesity, Metabolic Syndrome
Stages in the Evolution of Heart Failure
Stage B MI, LV Dysfunction, Valvular Disease
Stage C Dyspnea, Fatigue, Exercise
Tolerance
Clinical Characteristics
Stage D Symptoms at rest despite max. therapy
15
Stage A Risk Factor Reduction, ACE-I / ARB in DM
Vascular DZ
Stages in the Evolution of Heart Failure
Stage B ACE-I / ARB, B-Blockers
Stage C Pharmacologic Therapy, Devices
Treatment
Stage D Mechanical Devices, Heart Transplant
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New York Heart Association Classification
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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

18
Prognosis
50
lt30
Post MI n196
40
Cardiac Mortality
30
31-35
20
36-45
10
46-53
54-60
gt60
0
LVEF
Brodie B. et al, Am J Cardiol 1992691113
19

Treatment Objectives
20

• Treatment Modalities
• 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.

All
Selected Patients
21

Pharmacologic Therapy

• Diuretics
• ACE Inhibitors
• Beta Blockers
• Digitalis
• Spironolactone
• Others

22

• 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

23
Diuretics
Thiazides Inhibit active exchange of Cl-Na in
the cortical diluting segment of the ascending
loop of Henle
Cortex
K-sparing Inhibit reabsorption of Na in
the distal convoluted and collecting tubule
Loop of Henle
Loop diuretics Inhibit exchange of Cl-Na-K in
the thick segment of the ascending loop of Henle
Medulla
Collecting Tubule
24

• Diuretics Indications
• 1. Symptomatic HF, with Fluid Retention
• Edema
• Dyspnea
• Lung Crackles
• Jugular Distension
• Hepatomegaly
• Pulmonary edema (Xray)

25

• 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

26
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
27
Sharpe N. Heart failure. Martin Dunitz
200043 Kubo SH , et al. Am J Cardiol
1987601322 MRFIT, JAMA 19822481465 Pool
Wilson. Heart failure. Churchill Livinston
1997635
28

• 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 1998339387 Kramer et al. Am J Med
199910690
29
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 199286439
30

ACE-I Mechanism of Action
VASOCONSTRICTION
VASODILATATION
ALDOSTERONE
PROSTAGLANDINS
VASOPRESSIN
tPA
Kininogen
SYMPATHETIC
Kallikrein
Angiotensinogen
RENIN
BRADYKININ
Angiotensin I
A.C.E.
Kininase II
Inhibitor
ANGIOTENSIN II
Inactive Fragments
31
ACE-I Clinical Effects

• Improve Symptoms
• Reduce Remodeling / Progression
• Reduce Hospitalization
• Improve Survival

32
Mortality Reduction with ACE-I
Study ACE-I Clinical Seting CONSENSUS Enalapril CH
F 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
33
CONSENSUS
0.8
0.7
Placebo
0.6
plt 0.001
0.5
Probability of Death
0.4
0.3
Enalapril
0.2
0.1
0
0
12
11
10
9
8
7
6
5
4
3
2
1
Months
N Engl J Med 19873161429
34
SOLVD (Treatment)
p 0.0036
Placebo n1284
NYHA II-III EF lt 35
Mortality
Enalapril n1285
48
0
6
12
24
18
30
36
42
Months
N Engl J M 1991325293
35
SAVE
30
Placebo
Asymptomatic Ventricular Dysfunction Post MI
n1116
20
3 - 16 days post AMI EF lt 40 Captopril 12.5 -
150 mg/day
Mortality
Captopril
n1115
10
² -19
p0.019
0
4
3
0
1
2
Years
N Engl J Med 1992327669
36
AIRE
Placebo
30
HF S/P AMI
20
Mortality
Ramipril
10
p 0.002

0
30
24
12
18
0
6
Months
Lancet 1993342821
37
ACE-I Indications

• Symptomatic
• Heart Failure
• Asymptomatic
• Ventricular
• Dysfunction
• - LVEF lt 40
• Selected High
• Risk Subgroups

38

• 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

39
ACE-I Dose (mg) Initial Maximum Captopril
6.25 / 8h 50 / 8h Enalapril 2.5 / 12 h 10 to
20 / 12h 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 1.25
to 2.5 / day 10 / day
40

• ACE-I Adverse Effects
• Hypotension (1st dose effect)
• Worsening Renal Function
• Hyperkalemia
• Cough
• Angioedema

41

• ACE-I Contraindications
• Intolerance (angioedema, anuric renal failure)
• Bilateral Renal Artery Stenosis
• Pregnancy
• Renal Insufficiency (creatinine gt 2 mg/dL)
• Hyperkalemia (gt 5.5 mmol/l)
• Severe Hypotension

42

Angiotensin II Receptor Blockers (ARB)
RENIN
Angiotensin IANGIOTENSIN II

Angiotensinogen
ACE
Other pathways
AT1 Receptor Blockers
RECEPTORS
AT1
AT2
Vasoconstriction
Proliferative Action
Vasodilatation
Antiproliferative Action
43
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???

44
ARB Indications
Stage A B C
45
ARB Dose (mg)

• Initial Target
• Candesartan 4 8 / d 32 / d
• Losartan 25 50 / d 50 100 / d
• Valsartan 20 40 BID 160 BID

46
ß-Blockers Mechanism of action

• Density of ß1 Receptors
• Inhibit Cardiotoxicity of Catecholamines
• Neurohormonal Activation
• HR
• Antiischemic
• Antihypertensive
• Antiarrhythmic
• Antioxidant, Antiproliferative

47

ß-Blockers Clinical Effects

• Improve Symptoms (only long term)
• Reduce Remodelling / Progression
• Reduce Hospitalization
• Reduce Sudden Death
• Improve Survival

48
US Carvedilol HF
1.0
1.0
Carvedilol (n696)
0.9
0.9
Placebo (n398)
NYHA I-II
plt0.001
Survival
0.8
0.8
0.7
0.7
Risk Reduction 65
0.6
0
50
100
150
200
250
300
350
400
Days
NEJM 1996 334 1349-55
49
CIBIS-II
1
Bisoprolol 11.8
0.9
0.8
NYHA III-IV
Plt 0.00005
Survival
Placebo 17.3
0.7
0.6
0.5
0
600
400
200
800
Lancet 19993539
Days
50
MERIT-HF
Placebo
15
p0.0062
Metoprolol
10
NYHA II-IV
Mortality
5
Risk Reduction 34
0
0
3
6
9
12
15
18
21
Months
Lancet 1999 353 2001
51
COPERNICUS
100
90
NYHA III-IV
80
Survival
Carvedilol
70
p0.00014
60
Placebo
Risk Reduction 34
50
24
0
20
16
12
8
4
28
Months
NEJM 20013441651
52

CAPRICORN
1
HR 0.77 (0.60 - 0.98) plt0.031
0.95
0.9
Carvedilol 116 / 975 (12)
HF Post AMI
Survival
0.85
0.8
Placebo 151 / 984 (15)
0.75
0.7
0
0.5
1
1.5
2
2.5
Years
Lancet 20013571385
53
ß-Blockers Indications

• Symptomatic
• Heart Failure
• Asymptomatic
• Ventricular
• Dysfunction
• - LVEF lt 35
• After AMI

Stage A B C
54
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

55
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

56
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

57
ß-Blockers Contraindications

• Asthma (reactive airway disease)
• AV block (unless pacemaker)
• Symptomatic Hypotension / Bradycardia
• Diabetes is NOT a contraindication

58
Digitalis Mechanism of Action Blocks Na / K
ATPase gt Ca Inotropic effect Natriuresis
Neurohormonal control
NEJM 1988318358
59
Digitalis
-
Na-K ATPase
Na-Ca Exchange
Na
K
Na
Ca
Ca
Myofilaments
K
Na
CONTRACTILITY
60
Digitalis Clinical Effects

• Improve Symptoms
• Modest Reduction in Hospitalization
• Does Not Improve Survival

61

DIG
NYHA II-III
Mortality
Placebo n3403
p 0.8
Digoxin n3397
0
48
12
24
36
Months
N Engl J Med 1997336525
62
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
63
Digitalis Contraindications

• Digoxin toxicity
• Advanced A-V block without pacemaker
• Bradycardia or sick sinus without PM
• PVCs and VT
• Marked hypokalemia
• WPW with atrial fibrillation

64

Aldosterone Inhibitors
ALDOSTERONE
Spironolactone
-
Competitive antagonist of the aldosterone
receptor (myocardium, arterial walls, kidney)

• Retention Na
• Retention H2O
• Excretion K
• Excretion Mg2

• Collagen
• deposition
• Fibrosis
• - myocardium
• - vessels

Edema
Arrhythmias
65
RALES
Annual Mortality Aldactone 18 Placebo 23
NYHA III-IV
Aldactone
Survival
p lt 0.0001
Placebo
months
NEJM 1999341709
66

• Spironolactone Indications
• LV Dysfunction Early After MI
• Moderately Severe or Severe HF with Recent
  Decompensation
• Hypokalemia

67

• 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 gt5.5 mmol/L, reduce to 25 mg / 48h
• If K is low or stable consider 50 mg / day

68

NITRATESHEMODYNAMIC EFFECTS
1- VENOUS VASODILATATION
Preload2- Coronary vasodilatation Myocardial
perfusion 3- Arterial vasodilatation
Afterload 4- Others
Pulmonary congestionVentricular sizeVent. Wall
stressMVO2
69

VHefT-1 (Nitrates)
0.7
Placebo (273)Prazosin (183)Hz ISDN (186)
0.6
0.5
Probabilityof Death
0.4
0.3
0.2
0.1
0
0
6
12
18
24
30
36
42
Months
N Engl J Med 19863141547
70
V-HeFT II (Nitrate Hydralazine)
0.75
n 804
HZ ISDN
0,54
Probability of Death
0.50
0.47
p 0.016
0,48
0.36
0.42
Enalapril
0.25
0.31
0.25
0.13
0.18
0.09
p 0.08
0
60
0
12
24
48
36
N Engl J Med 1991 325303
Months
71
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)

72

• Positive Inotropes
• Digitalis
• Sympathomimetics
• Catecholamines
• B-adrenergic agonists
• Phosphodiesterase inhibitors
• Amrinone, Milrinone, Enoximone
• Calcium sensitizers
• Levosimendan, Pimobendan

73
Positive Inotropic Therapy

• May increase mortality
• Exception Digoxin, Levosimendan
• Use only in refractory CHF
• NOT for use as chronic therapy

74
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

75

• 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

76

• Heart Transplant Indications
• Refractory cardiogenic shock
• Documented dependence on IV inotropic support to
  maintain adequate organ perfusion
• Peak VO2 lt 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

77

• Supraventricular Arrhythmias
• Risk of embolization (AF)
• Anticoagulation in AF
• Systolic diastolic dysfunction
• Digoxin, beta blockers
• Amiodarone if b-blocker ineffective/ contraind.

78

• 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 lt 30 and mild - moderate HF symptoms

79

• 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

80

• Diastolic Heart Failure
• Treat as HF with low LVEF
• Control
• Hypertension
• Tachycardia
• Fluid Retention
• Myocardial Ischemia
• Ongoing Research

81
Treatment Summary
Symptoms Morbidity Mortality
Increase Dose of ACEI No effect ? 10-15 No effect
Add ARB ? ? 10-15 No effect
Add ß-blocker ? ? 20-35 ? 35
Add Aldactone ? ? 20 ? 16-25
Add ISDN Hydralazine ? ? 30 ? 40
AHA Scientific Sessions, 2004 (Lachel et al)
82
(No Transcript)