Transcript Heart Failure: A Growing Burden

GUIAS PARA EL MANEJO DEL
FALLO CARDIACO
RAFAEL E. CALDERON,MD.
CARDIOLOGIA DE TRANSPLANTE Y FALLO CARDIACO
OCTUBRE DEL 2002
Cost* of Heart Failure to Society
$22.5 billion
Hospital/Nursing home
2.2
15.5
Home health/
Other medical durables
2.2
Indirect costs
1.5
Healthcare providers
Drugs
1.1
*Direct and indirect costs in billions of $; estimated for year 2000
AHA. 2000 Heart and Stroke Statistical Update
Predisposing Factors
HTN
Environmental
Genetic
HTN
Toxins/drugs
(EtOH)
Valvular
disease
Unknown Infections
Age
Metabolic
(Diabetes)
Cardiomyopathy
MI
HF
HFSA. Pharmacotherapy 2000;20:495
Risk Factors, Ischemia, and Heart
Failure in the Cardiovascular Continuum
Coronary
thrombosis
Myocardial ischemia
CAD
MI
Arrhythmia
Loss of
muscle
Neurohormonal
activation
Sudden
death
Remodeling
Atherosclerosis
LVH
Risk factors
•Hyperlipidemia
•HTN
•Diabetes
•Insulin resistance
Ventricular
dilation
HF
Death
Adapted with permission from Dzau V, Braunwald E. Am Heart J 1991;121:1244
Pathophysiologic Effects of
Angiotensin II
PAI-1/
thrombosis
Abnormal
vasoconstriction
Ang
II
Platelet
aggregation
Contractility
Superoxide
production
Activate
SNS
Vascular
Collagen
Myocyte
smooth
growth muscle growth
Aldosterone
Vasopressin
Endothelin
Remodeling
Guide for Heart Failure Therapy
Goal: Prolong life and improve its quality
Objectives:
• Slow progression of underlying disease(s)
• Improve hemodynamics
• Improve neurohormonal profile
• Prevent sudden death
• Decrease symptomatic arrhythmias
• Relieve symptoms and improve exercise tolerance
• Decrease ER visits, hospitalizations, and costs
HFSA. Pharmacotherapy 2000;20:495
Why Symptom Relief is Not Enough
Heart failure is more than a symptomatic disease
Produces symptoms, limits functional capacity, and impairs
quality of life
Heart failure is a progressive disease
Worsening symptoms and clinical deterioration, repeated
hospitalization, and death
Death occurs frequently even in the presence of minimal
symptoms or the absence of progressive symptoms
Symptoms do not always correspond with ejection fraction
Evolution of Drug Therapies for CHF
18th
Century
19th
Century
•Digitalis
•Weak
diuretics
1960s
1970s-1980s
•Thiazides •Vasodilators
and
•IV inotropics
furosemide
1980s
1990s
•ACE
•Beta-blockers
inhibitors
–Potential role for
Angiotensin II
antagonists
–Aldosterone
antagonists
Systemic Effects of RAS Activation in
CHF
Schematic Representation of Mortality
in Heart Failure Patients
60
V-HeFT II (Class II–III)2
n=804
trend toward  death
CONSENSUS I (Class IV)1
n=253
27%  mortality
P=0.003
40
SOLVD-Treatment
(Class II–III)3
28%  mortality
P=0.016
Mortality
rate
(%)
20
n=2569
16%  mortality
P=0.0036
SOLVD-Prevention (Class I–II)4
n=4228
trend toward  death
0
0
6
12
18
24
30
36
42
48
54
60
Months
1CONSENSUS Trial Study Group. N Engl J Med 1987;316:1429; 2Cohn JN et al. N Engl J Med 1991;325:303;
3SOLVD Investigators. N Engl J Med 1991;325:293; 4SOLVD Investigators. N Engl J Med 1992;327:685
ACE Inhibitors in CHF:
Summary of Key Points
• Consistent evidence that neurohormonal
•
•
blockade alters natural history of CHF
ACE inhibitors improve survival across
entire heart failure spectrum - mild,
moderate, severe
Ace inhibitors delay progression of
asymptomatic LV dysfunction to overt CHF
The Case for ß-Blockade in Heart Failure
Neurohormonal activation underlies disease
progression and provides basis for treatment
selection
Weight of data for ß-blockade equals or exceeds that
of ACE inhibitors
ß-Blockade is added to ACE inhibitors for more
complete neurohormonal blockade
Carvedilol blocks ß1-, ß2-, and 1-receptors and is
the only agent with ß-blocking properties approved
and formulated for use in heart failure
ß-Blockers in Heart Failure:
Key Clinical Trials
TRIAL
DRUG
US Carvedilol Carvedilol
(n = 1094)
TARGET DAILY
DOSE
RISK REDUCTION /
TOTAL MORTALITY
50-100 mg
65%
(P <0.001)
MERIT-HF
(N = 3718)
Metropolol
200 mg
34%
(P = 0.0062)
CIBIS II
(n = 2647)
Bisoprolol
10 mg
33%
(P <0.0001)
Copernicus
(n = 2289)
Carvedilol
50 mg
35%
(P = 0.0014)
MERIT-HF
Cardiovascular Mortality
20
Percent of patients
Risk reduction: 38%
P=0.00003
15
Placebo
TOPROL-XL
Risk reduction: 38%
10
P = .00003
5
0
0
3
6
9
12
15
18
21
Months of follow-up
MERIT-HF Study Group. Lancet. 1999;353:2001-2007.
MERIT-HF
Sudden Death
12
Placebo
9
% of
patients
TOPROL-XL
6
Risk reduction: 41%
P = .0002
3
3
6
9
12
15
18
Months of follow-up
MERIT-HF Study Group. Lancet.
1999;353:2001-2007.
21
DIG Study: Effect of Digoxin vs Placebo on
Mortality in Patients With CHF and LVEF 
45%
50
40
30
Placebo
20
10
P=0.80
Digoxin
0
0
4
8 12 16 20 24 28 32 36 40 44 48 52
The Digitalis Investigation Group. N Engl J Med 1997;336:525-533.
RADIANCE: Effect of Digoxin Withdrawal in
Patients Optimally Treated With ACEIs
• Risk of
deterioration
 6-fold
•  Exercise
tolerance
•  Ejection
fraction
•  Quality of life
0.3
0.25
Placebo
(n=93)
Probability 0.2
of
worsening 0.15
heart
failure
0.1
P<0.01
0.05
Digoxin (n=85)
0
Packer M, et al. N Engl J Med 1993;329:1-7.
0
20
40
60
80
Days after randomization
100
RALES: Aldosterone Receptor Blockade
Improves Outcomes in Severe Heart Failure
1
0.9
Spironolactone
0.8
Probability
of Survival 0.7
(%)
0.6
Placebo
0.5
0.4
0
RALES=Randomized
Aldactone Evaluation Study
3
6
9
12 15 18 21 24 27 30 33 36
Months
Pitt B, et al N Engl J Med 1999;341:709-17
Valsartan in Heart Failure
Trial (Val-Heft)
• Ace inhibitors are effective treatment for HF, post-MI,
diabetic nephropathy, and atherosclerosis, but do not fully
suppress RAAS
• The RAAS exerts deleterious effects on the development
and progression of HF
• Addition of ARBs to usual therapy, including ACE inhibitors,
is rational therapeutic approach
• ARBs inhibit biologic effects of Ang II more completely than
ACE inhibitors
• ARBs potentially increase AT2 receptor stimulation resulting
in increased bradykinin and NO production
Heart Failure Hospitalizations
1.000
100
Event-free Probability
0.961
95
90
RR=27.5 %
P< 0.00001
0.923
0.884
85
80
0.846 75
0.807 70
0.769
65
0
0.730
0
Valsartan
0
3
3
6
6
9
9
12
12
Months
15
15
Placebo
18
18
21
21
24
24
27
27
Cohn JN. AHA 2000
General Measures for the
Management of Heart Failure
Decrease risk of
new cardiac injury
Smoking cessation; weight reduction in
obese patients; control  BP, lipids,
diabetes; discontinue alcohol use
Maintain fluid
balance
Moderate salt restriction (to < 3 grams
daily); daily weight measurement
Improve physical
conditioning
Moderate exercise to prevent physical
deconditioning
Avoid
Antiarrhythmic agents to suppress
asymptomatic ventricular arrhythmias,
most calcium antagonists, NSAIDs
Steering Committee and Membership of the Advisory Council to Improve Outcomes Nationwide in heart Failure
Am J Cardiol. 1999;83 (Suppl 2A): 1A-39A
Gottipaty et al:
Proportional Mortality Increase
• VEST study analysis
• NYHA Class II-IV
•
•
•
patients
3,654 ECGs digitally
scanned
Age, creatinine, LVEF,
heart rate, and QRS
duration found to be
independent predictors
of mortality at 1 year
Relative risk of widest
QRS group 5x greater
than narrowest
QRS Variability in
Congestive Heart Failure:
Mean change in
QRS (msec) over time
Should QRS Criteria for Cardiac
Resynchronization Therapy Be Expanded?
(n = 31)
Aranda, et al
HFSA Sept 2001
50
43.1
40
30
15.8
20
10
0
Pts with QRS
< 130 0
msec
Pts with QRS
 1300msec
Multicenter InSync Randomized
Clinical Evaluation
Results of a Randomized, Double-Blind,
Controlled Trial to Assess Cardiac
Resynchronization
Therapy in Heart Failure Patients
Presented by William T. Abraham, MD
For the MIRACLE Investigators at the
Late Breaking Clinical Trials II Session,
American College of Cardiology
Orlando, FL; March 20, 2001
Unanswered Questions
• Which subset of patients can benefit
•
•
•
from biventricular pacing?
What are the long-term hemodynamic
and structural consequences of CRT?
Is there potential to increase ischemic
burden in patients with ischemic
cardiomyopathy?
Will cardiac resynchronization therapy
allow for increased use of beta-blocker
therapy in patients with heart failure?
Recommendations
• Class I: There is evidence and/or general agreement
that a given procedure/therapy is useful and
effective.
• Class II: There is conflicting evidence and/or a
divergence of opinion about the usefulness/efficacy
of performing the procedure/therapy
– Class IIa: Weight of evidence/opinion is in favor of
usefulness/efficacy.
– Class IIb: Usefulness/efficacy is less well established by
evidence/opinion.
• Class III: There is evidence and/or general
agreement that procedure/therapy is not
useful/effective and in some cases may be harmful.
Levels of Evidence
• Level A:
The data was derived from
multiple randomized clinical trials
• Level B:
Data were derived from single
randomized trial or nonrandomized
studies
• Level C:
Consensus of opinion
Clinical Assessment
• Complete history (Class I Level of evidence C):
comorbid conditions, cardiotoxic agents, STD’s,
magnitude and duration of symptoms and family
history
• Physical exam (Class I Level of evidence C):
Jugular venous pressure as ongoing assessment of
volume status and S3
• Signs of hypoperfusion narrow pulse pressure, cool
extremities, altered mentation, Cheynes-Stokes
respiration, resting tachycardia.
Clinical Assessment
• Laboratory work up
– CBC, U/A, SMA 20, TSH, CXR and 12 lead EKG (Class I
Level of evidence C)
– Serial monitoring of electrolytes and renal function
(Class I Level of evidence C)
– Screening
for
hemochromatosis,
ANA
levels,
rheumatoid factor, urinary vanillylmandelic acid and
metanephrines in selected patients (Class IIa Level of
evidence C)
– HIV status (Class IIb Level of evidence C)
– Routine measurement of circulating levels of
norepinephrine or endothelin (Class III Level of
evidence C)
– Routine Holter monitoring or signal averaged
electrocardiography (Class III Level of evidence C)
Clinical Assessment
• Two-dimensional echocardiogram
with Doppler flow. Single most useful
diagnostic test.
– Evaluation of LV function and other structural
heart disease (Class I Level of evidence C)
– Asymptomatic first degree relatives of
idiopathic DCMP patients (Class IIa Level of
evidence C)
– Repeat measurement of EF in patients with
change in clinical status (Class IIa Level of
evidence C)
Clinical Assessment
• Functional capacity assessment during
initial and follow up visits
– Ability to perform routine and desired ADL’s (Class I Level of
evidence C)
– Maximal exercise testing with measurement of respiratory
gas exchange and/or blood oxygen saturation to help
determine whether HF is cause of exercise limitation when
the contribution of HF is uncertain (Class IIa Level of
evidence C)
– Maximal exercise testing with measurement of respiratory
gas exchange to identify high risk patients who are
candidates for cardiac transplantation or other advanced
treatments (Class IIa Level of evidence B)
– Maximal exercise testing with measurement of respiratory
gas exchange to facilitate prescription of exercise program
(Class IIb Level of evidence C)
Clinical Assessment
• Noninvasive testing
– Noninvasive imaging to detect ischemia and
viability in patients with known CAD and no
angina who are being considered for
revascularization (Class IIa Level of evidence C)
– Noninvasive imaging to define the likelihood
of CAD in patients with LV dysfunction (Class
IIb Level of evidence C)
Clinical Assessment
• Cardiac Catheterization with coronary
arteriography
– Patients with angina who are candidates for
revascularization (Class I Level of evidence B)
– Patients with chest pain who have not had evaluation
of their coronary anatomy and who have no
contraindications to coronary revascularization (Class
IIb Level of evidence C)
– Patients with known or suspected CAD but without
angina who are candidates for revascularization (Class
IIb Level of evidence C)
– Repeat study or repeat noninvasive testing for
ischemia in patients for whom CAD has been
previously excluded as cause of LV dysfunction (Class
III Level of evidence C)
Clinical Assessment
• Endomyocardial Biopsy overall
usefulness is unclear
– Patients suspected of having inflammatory or
infiltrative disorder of the heart (Class IIb Level of
evidence C)
– Used to confirm disorders that may disqualify a
patient for transplant (amyloidosis) or identify
giant-cell myocarditis which due to rapid
progression and poor response to therapy
mandates immediate transplantation.
– Routine evaluation of patients with HF (Class III
Level of evidence C)
Staging of HF
• A new approach that emphasized both
the evolution and progression of HF
• It reliably and objectively identifies
patients in the course of their disease
• Links treatments that are appropriate at
each stage of HF
• It is intended to complement not
substitute NYHA, which subjectively
gauges severity of symptoms
Staging of HF
Staging of HF and Therapy
Stage A of HF and Therapy
• High risk of developing HF.
– Control systolic and diastolic BP (Class I Level of evidence
A)
– Adequate control of DM. (not yet shown to reduce
subsequent HF)
– Treatment of lipid disorders in accordance with guidelines as
patients with atherosclerotic disease are likely to develop HF
(Class I Level of evidence B)
– Treat Thyroid disease (Class I Level of evidence C)
– Periodic evaluation for signs and symptoms of HF (Class
I Level of evidence C)
Stage A of HF and Therapy
– Avoidance of cardiotoxic agents and behaviors such as
smoking, illicit drug use and alcohol consumption.(Class
I Level of evidence C)
– Ionizing
radiation
chemotherapeutic agents
dose cyclophosphamide
trastuzumab.
– Control ventricular rate of
of evidence B)
to
mediastinum
and
such as anthracyclines, high
and the monoclonal agent
tachyarrhythmias (Class I Level
– ACE inhibition in patients with history of atherosclerotic
vascular
disease,
DM,
HBP
and
associated
cardiovascular risk factors (Class I Level of evidence B)
Stage B of HF and Therapy
• LV dysfunction without HF symptoms.
– Patients with AMI should receive thrombolytic or
undergo PTCA to decrease risk of developing HF. ACEI
regardless of EF and even if ischemic episode is remote
(Class I Level of evidence A)
and /or beta-blocker
regardless of EF (Class I Level of evidence A) improve
survival.
– Long term use of ACEI has been shown to delay onset of
HF symptoms in patients with low EF independently of
MI or not (Class I Level of evidence B)
– Beta blockers independent of whether the patient has
had MI should be given in low LVEF (Class I Level of
evidence B)
Stage B of HF and Therapy
– Valve replacement or repair for patients with
hemodynamically
significant stenosis or
regurgitation (Class I Level of evidence B)
– Long term treatment with vasodilators in
severe aortic regurgitation has not been shown
to reduce risk of HF or death (Class IIb Level of
evidence B)
– Treatment with digoxin in asymptomatic
patient with LV dysfunction who are in sinus
rhythm is not recommended (Class III Level of
evidence C)
Stage C of HF and Therapy
• LV dysfunction with current or prior
symptoms.
–
–
–
–
Sodium restriction.
Daily weight.
Influenza and pneumococcal vaccination.
Physical activity exercise program. (Class IIa Level of
evidence A)
– Avoidance of
NSAIDs (including COX2), calcium
channel
blockers
(
except
amlodipine)
and
antiarrhythmic agents (except amiodarone). (Class I
Level of evidence B)
– Monitor potassium (3.8-5.2mmol per
magnesium.
– Patient education and close supervision.
L)
and
Stage C of HF and Therapy
Stage C of HF and Therapy
• Diuretics. For fluid retention. (Class I Level
of evidence A)
– Inhibit reabsorption of sodium or chloride at specific
sites in the renal tubule.
– Loop diuretics excrete up to 20-25% Na, enhance free
water clearance and remain effective unless severe
renal impairment.
– No long term studies effects on morbidity and mortality
are not known
– Produce symptomatic relief more rapidly than any other
drug.
– Risk of use is electrolyte depletion, hypotension and
azotemia.
Stage C of HF and Therapy
• ACE inhibitors. (Class I Level of evidence A)
– Not only interferes with RAS but potentates action of
kinins and kinin-mediated prostaglandin.
– Alleviate symptoms, improve clinical status, reduce risk
of death and of hospitalization.
– Contraindicated if angioedema or pregnant .
– Fluid retention can blunt effects and fluid depletion can
potentate adverse effects (Hypotension, hyperkalemia,
renal failure)
– Cough. All other causes must be excluded medication
withdrawn with improvement after 1-2 weeks and
reappearance after rechallenge with another ACEI.
Stage C of HF and Therapy
• Beta-blockers principally inhibit effects of
sympathetic nervous system and should be
given to all patients with symptoms (Class I
Level of evidence A)
– Alleviate symptoms, improve clinical status, reduce risk
of death and of hospitalization.
– Diuretics are needed to maintain sodium balance and
prevent fluid retention that can accompany initiation of
beta-blocker.
– Should be given only if no or only minimal evidence of
fluid retention and no recent use of intravenous positive
inotropic agent.
Stage C of HF and Therapy
• Beta-blockers
– A patient who has been using medication for more than
3 months and has acute decompensation should not be
taken off medication and diuretics should be adjusted.
If decompensation is cause due to hypoperfusion then
medication should be stopped and positive inotropic
agent that doesn’t mediate its effects through beta
receptor is preferred.
– Side
effects
include
fatigue,
fluid
retention,bradychardia, heart block, and hypotension.
– Should not be given to patients with hyperactive airway
disease yet should be given to COPD patients.
Stage C of HF and Therapy
• Digitalis (Class I Level of evidence A)
– Inhibits Na-K ATPase
• In cardiac cells causing increased contractility
• Vagal afferent fibers sensitize carotid baroreceptor which
reduces sympathetic out flow of CNS
• Kidney reduces renal tubular reabsorption of Na which leads to
suppression of of renin secretion
– Improves symptoms, exercise tolerance and quality of
life yet little effect on mortality
– Dose should be of 0.125-0.25mg QD, without loading
and lower if patient is over age 70, has renal
impairment or low lean body mass
– Serum levels are followed for purpose of toxicity and
not to guide therapy
Stage C of HF and Therapy
• Spironolactone (Class IIa Level of
evidence B)
– Low doses reduced risk of mortality in patents
with current or recent class IV symptoms
– Effects were most marked in those taking
digitalis and beta blockers
– Role in mild to moderate HF not clear and use
cannot be recommended
– Risk of hyperkalemia and painful gynecomastia
Stage C of HF and Therapy
• Angiotensin receptor blocker
– Should not be considered superior or equivalent
to ACEI (Class III Level of evidence B)
– Added to therapy before a beta-blocker (Class
III Level of evidence A)
– Should not be added to therapy if taking an
ACEI and beta-blocker
– Should be given if ACEI intolerant (Class IIa
Level of evidence A)
Stage C of HF and Therapy
• Hydralazine and nitrate combination should
•
be given only if ACEI intolerant and patient
on beta-blocker, diuretic and digitalis (Class
IIa Level of evidence B) and should no be
added if ACEI in use (Class IIb Level of
evidence B)
Long term intermittent intravenous positive
inotropic therapy has been associated with
increased mortality and should not be used
(Class III Level of evidence C). Continuous
infusion for palliation of stage D symptoms
is Class IIb Level of evidence C yet is
commonly used in patients awaiting
transplant.
Stage D of HF and Therapy
• Refractory End stage HF
– Must be considered for specialized treatment strategies,
such as mechanical circulatory support, continuous
inotropic therapy, transplantation (Class I Level of
evidence B), referral to a specialized HF program (Class
I Level of evidence A) or hospice care.
– Control of fluid retention with increments of dose or
adding second diuretic (metolazonel). Increases in BUN
and creatinine are tolerated and should not guide
therapy. If refractant to diuretics ultrafiltration may be
needed.Patients should not be discharged until
euvolemia is achieved. (Class I Level of evidence B)
– All previous stage class I recommendations (Class I
Level of evidence A,B and C)
Stage D of HF and Therapy
Patient Subgroups
• Women are the majority of patients in general
population with HF yet are underrepresented in most
studies which doesn’t allow for treatment conclusions
to be made. Have diastolic dysfunction most often.
• HF is more common among black patients and
progresses more rapidly and may derive less benefit
of ACEI. Almost 50% of Asians can develop cough
related to ACEI.
• HF is a disease of the elderly affecting 6-10% of
population over age 65. Diastolic dysfunction is a
major cause. Diminished response to diuretics ACEI
and inotropic agents.
Diastolic Dysfunction
Therapy of Diastolic Dysfunction
• Control systolic and diastolic BP (Class I Level of
evidence A)
• Control ventricular rate in atrial fibrillation (Class
I Level of evidence C)
• Diuretics to control pulmonary congestion and
peripheral edema (Class I Level of evidence C)
• Coronary revascularization I patients with CAD in
whom ischemia is judged to have effect on
diastolic dysfunction (Class IIa Level of evidence
C)
Therapy of Diastolic Dysfunction
• Restoration of sinus rhythm in atrial
fibrillation (Class IIb Level of evidence C)
• Use of beta blockers, ACEI, ARB, CCB in
patients with controlled hypertension to
minimize symptoms of HF (Class IIb Level
of evidence C)
• Digitalis to minimize symptoms of HF
(Class IIb Level of evidence C)
Treatment of CHF in the Year 2001
Inactive
OVERTURE
NEP
ACE
Bradykinin
ANP
BNP
Angio 1 SOLVD
Inactive
Angio 2
Brain
CONSENSUS II
ATLAS
SAVE
Elite I, II
Val-HeFT
Kidney
NATRE-COR
Inotropes
DIG TRIAL
VEST
PROMISE
OPTIME-CHF
PROVED
NO
EDRF
Na H2O
Vasodilation
Hypertrophy
CO
Vascular
Catecholamines ADH
Aldosterone
CIBIS II
MERIT-HF
BEST
COPERNICUS
Positive Effect
Neutral Effect
Unknown Effect
Negative Effect
RALES
BP
Na
Hypertrophy
HR
Endothelin
•
EECP
• The CorCap (Acorn)
• Resembles a net that is
placed around and attached to
the heart.
Cardiology Today,October 2002
Cardiology today, october 2002.
The End