Transcript Congestive Heart Failure

Heart Failure
Current Concepts
Howard M. Weinberg, D.O.
F.A.C.C.
Cardiac Architecture

Ultrastructure
1. 75% total volume of the heart is made up of
cardiomyocyte
2. Contractile proteins lie within the cardiomyocyte
A. Ventricular and atrial myocytes
B. Myofibrils form myocytes(contractile
elements)
C. Myofibers are groups of myocytes.
Contractile Proteins
1.
2.
Actin and Myosin
Calcium interacts with Troponin C
relieves the inhibition caused by
Troponin I
Cardiac Cycle
Three Phases:
The Cardiac Cycle
LV CONTRACTION
1) LV Contraction
2) LV Relaxation
3) LV Filling
Isovolumic contraction(b)
Maximal Ejection ©
LV Relaxation
Start of relaxation and
reduced ejection (d)
Isovolumic relaxation(e)
LV Filling: rapid phase (f)
Slow LV Filling (g)
Atrial systole( a)
See Wiggers Diagram
Frank-Starling Relationship
A.
B.
Preload: Load before contraction(venous
return)
Afterload: Load which the LV contracts
against
Starling Curve
HF Defined
“Heart failure is a complex 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 with an increase in intracardiac
chamber pressure”
Hunt SA et al. Circulation. 2001;104:2996
Clinical Aspects of Heart Failure

Backward Heart Failure
LVEDP and LVEDV increase
 LAP and LAV increase(atria contracts for
C.O.)
 Venous and PCWP increase
 Transudation of fluid from capillary bed
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Clinical Aspects of Heart Failure
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Forward Heart Failure
Decrease C.O.= decrease perfusion to vital
organs
 Increase Na and Water retention
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Symptoms of Heart Failure
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Exertional Dyspnea
Orthopnea-Sx in the recumbent position
Paroxysmal Nocturnal Dyspnea
Theory: 1. Slow resorption of interstial
fluid
2. Reduced adrenergic support
at night
3. Normal nocturnal
depression of the respiratory
center
Framingham Criteria for CHF
Cardiac vs Pulmonary Dyspnea
Frequent coughing
 Cough production
 Fever
 Diaphoresis
 Response to Tx
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Diastolic Heart Failure
1.
2.
3.
4.
5.
1/3 of pts. have primary diastolic HF
(normal or near normal LV function)
1/3 combined systolic and diastolic HF
Altered ventricular relaxation(inactivation
of contraction)
Alteration of ventricular filling
Some causes: myocardial ischemia,
restrictive cardiomyopathy,pericardial
disease
Diastolic Heart Failure
Impaired ability to accept blood and relax
during diastole
 Both types increase with age, African
Americans
 40-70% incidence more often female,
obese, older HTN and less likely to have
CAD
 Less symptomatic and lower morbidity and
mortality
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High Output Failure
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Usually occurs with some underlying heart
disease
Clinical conditions:
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Anemia
Systemic Ateriovenous Fistula-dialysis/trauma
Hyperthyroidism
Beriberi
Pagets
Multiple myeloma/Pregnancy/Carcinoid/ renal disease
Obesity/polycythemia vera
Disease Progression of HF:
ACC/AHA HF Stages
D
C
B
A
Refractory
End-Stage HF:
Marked symptoms
at rest despite maximal
medical therapy
Symptomatic HF: Known structural
heart disease, shortness of breath and
fatigue, reduced exercise tolerance
Asymptomatic LVD: Previous MI, LV systolic
dysfunction, asymptomatic valvular disease
High Risk: Hypertension, coronary artery disease, diabetes,
family history of cardiomyopathy
Yancy CW, Strong M. Prim Care Spec Ed. 2002;6:15
Epidemiology
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Only major
cardiovascular
disorder increasing in
incidence and
prevalence
Leading cause of
hospitalization in >65
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1/3 hospitalized
patients readmitted in
90 days
5% of all hospital
admissions
Heart Failure is a Major and Growing Public
Health Problem in the U.S.
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Approximately 5 million patients in this country have
HF
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Over 550,000 patients are diagnosed with HF for the
first time each year
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Primary reason for 12 to 15 million office visits and
6.5 million hospital days each year
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In 2001, nearly 53,000 patients died of HF as a
primary cause
Mortality/Morbidity
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Despite therapeutic
advances, the 1 year
mortality for NYHA
class IV approaches
40%
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Impaired Quality of
life.
Psychological distress
Reduced social
functioning
49% admitted after
an emotional event
Prevalence of HF Increases
With Age
10
Males
Population (%)
8
Females
6
4
2
0
20–24
25–34
35–44
45–54
55–64
Age (yr)
US, 1988–1994
AHA. Heart Disease and Stroke Statistics—2004 Update
65–74
75+
Number of Patients
With HF Increasing
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1979–2001
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Hospital discharges from HF rose 164% from
377,000 to 995,000
Deaths increased 155%
As US population ages, number of patients
with HF expected to double in 30 yr
AHA. Heart Disease and Stroke Statistics—2004 Update
Massie BM et al. Am Heart J. 1997;133:703
Natural History of HF
100%
Survival (%)
Progression
Mechanism of Death
Sudden death 40%
Worsened HF 40%
Other
20%
Annual Mortality
0%
<5%
10%
20%–30%
30%–80%
Asymptomatic
Mild
Moderate
Severe
LV Dysfunction and Symptoms
Treatment of Heart Failure
Non-surgical
Specialty Clinics
Lifestyle Modification
Pharmacological
 Surgical
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Contributing Factors to ADHF
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Cardiovascular Factors
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Superimposed ischemia or infarction
Uncontrolled hypertension
Unrecognized primary valvular disease
Worsening secondary mitral regurgitation
New onset or uncontrolled atrial fibrillation
Excessive tachycardia or bradycardia
Pulmonary embolism
Stevenson LW et al. Am Heart J. 1998;135:293
Contributing Factors to ADHF
cont'd
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Systemic Factors
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Inappropriate medications
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Superimposed infection
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Anemia
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Uncontrolled diabetes
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Thyroid dysfunction
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Electrolyte abnormalities
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Pregnancy
Stevenson LW et al. Am Heart J. 1998;135:293
Contributing Factors to ADHF
cont'd
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Patient-Related Factors
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Medication nonadherence
Dietary indiscretion
Alcohol consumption
Substance abuse
Stevenson LW et al. Am Heart J. 1998;135:293
Proven Outcomes for HF
Therapies
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Improve Survival
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ACE inhibitor
ARB
Beta blocker
Aldosterone receptor
antagonist
Hydralazine/longacting nitrates
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Reduce Hospitalization
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ACE inhibitor
ARB
Beta blocker
Aldosterone receptor
antagonist
Hydralazine/long-acting
nitrates
Digoxin
Surgical/Interventional Therapy
Cardiac Resynchronization Therapy
 Revascularization
 Value repair/replacement
 Cardiomyoplasty
 Ventricular Reduction
 Left Ventricular Assist Devices
 Transplant
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Ventricular Remodeling
Ventricular Remodeling After Acute Infarction
Global remodeling
(days to months)
Initial infarct
Expansion of infarct
(hours to days)
Ventricular Remodeling in Diastolic and Systolic HF
Normal heart
Dilated heart
(systolic HF)
Hypertrophied heart
(diastolic HF)
Jessup M et al. N Engl J Med. 2003;348:2007
HF Therapy
PLUS inotropes,
transplant, ventricular
assist device
PLUS ACE inhibitors, beta blockers,
diuretics, digoxin, aldosterone receptor
antagonists, dietary salt restriction
PLUS ACE inhibitors, beta blockers in
appropriate populations
Treat hypertension and lipids, smoking cessation,
exercise, limit alcohol, ACE inhibitors in appropriate
populations
Yancy CW, Strong M. Prim Care Spec Ed. 2002;6:15
Approach to the Patient with
CHF
Assessment of LV Function
Echo, Muga
Ejection Fraction
< 40%
Assessment of Volume Status
Signs and sympoms of fluid retention
No Signs and Symptoms of fluid retention
Diuretic
titrate to euvolemia
Ace-Inhibitor
Beta Bocker
Digoxin
Ace-Inhibitor
Beta Bocker
Digoxin
Neurohormonal Activation
in Heart Failure
Myocardial Injury
(CAD,HTN,CMP)
LV Dysfunction
Increase wall stress
Activation of RAS and SNS
LV Remodeling
and
progressive LV Dysfunction
Morbidity/Mortality
Arrhythmias
Pump Failure
Fibrosis, apoptosis, hypertrophy
cellular/molecular alterations,
myotoxicity
Peripheral vasoconstriction
Hemodynamic alterations
Heart Failure Symtoms
Dyspnea
Fatigue ,Edema
Chest Congestion
Background on Remodelling
Acute infarction
(hours)
Infarct expansion
(hours to days)
Global remodelling
(days to months)
Improvement of LV remodelling has been
associated with improvement in mortality and
morbidity outcomes in CHF
B-Adrenergic Receptor Blockers
Improve survival
 Improve ejection fraction
 Remodeling
 Quality of life
 Reduce SCD
 Inhibiting adverse effects of the
sympathetic nervous system
 Diminish RAAS activation
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All-Cause Mortality: MERIT-HF
Cumulative Mortality (%)
20
Placebo
Metoprolol CR/XL
15
P=0.0082 (adjusted)
P=0.00009 (nominal)
10
5
0
0
3
6
9
12
15
Follow-up (mo)
MERIT-HF Study Group. Lancet. 1999;353:2001
18 21
Survival (% of Patients)
With Severe HF:
COPERNICUS
100
Carvedilol
(n = 1156)
90
80
Placebo
(n = 1133)
70
60
P=0.0014 (adjusted)
P=0.00013 (unadjusted)
0
0
3
6
9
12 15 18 21
Months
No. of Patients at Risk
Placebo
1133
937
Carvedilol
1156
947
Packer M et al. N Engl J Med. 2001;344:1651
703
733
580
620
446
479
286
321
183
208
114
142
Angiotensin-Converting Inhibitors
Decrease conversion of angiotensin I-II
 Improve survival
 Decrease rate of hospitalization
 Improve symptoms
 Inhibit neurohormonal activation
 Reverse remodeling
 Decrease incidence of SCD?
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Cumulative Mortality in Patients
With Symptomatic HF: SOLVD
Mortality (%)
50
P=0.0036
40
(n = 1284)
Placebo
30
Enalapril
(n = 1285)
20
10
0
0
6
12
18
24
30
36
42
48
Months
No. of Patients at Risk
Placebo
Enalapril
1284 1159 1085
1285 1195 1127
1005 939 819 669
1069 1010 891 697
P=0.0036 for comparison between groups by log-rank test
SOLVD Investigators. N Engl J Med. 1991;325:293
487
526
299
333
DIGOXIN
NEUROHORMONAL EFFECTS
Plasma Noradrenaline
Peripheral nervous system activity
RAAS activity
Vagal tone
Normalizes arterial baroreceptors
DIGOXIN
EFFECT ON CHF PROGRESSION
30
Placebo n=93
DIGOXIN
Withdrawal
%
WORSENING
OF CHF
20
p = 0.001
DIGOXIN: 0.125 - 0.5 mg /d
(0.7 - 2.0 ng/ml)
10
EF < 35%
Class I-III (digoxin+diuretic+ACEI)
Also significantly decreased exercise
time and LVEF.
0
RADIANCE
N Engl J Med 1993;329:1
DIGOXIN n=85
0
20
40
60
Days
80 100
All-Cause Mortality: Digoxin
Mortality From Any Cause (%)
50
P=0.80
40
30
20
Placebo
10
Digoxin
0
0
4
No. of Patients at Risk
Placebo
Digoxin
3403 3239 3105
3397 3269 3144
8
12
16
20
24
28
32
36
40
44
48
52
Months
2976 2868 2758 2652 2551 2205
3019 2882 2759 2644 2531 2184
DIG Investigation Group. N Engl J Med 1997;336:525
1881
1840
1506
1475
1168
1156
734
737
339
335
ARB in Heart Failure
(meta-analysis)
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17 Trials, 12,469pts (JACC Feb 2002)
No superiority of ARBs in reducing all-cause
mortality or hospitalizations for heart failure
Poss. benefit with combination ace inhibition
Beneficial for pts intolerant to ace inhibition
ALDOSTERONE INHIBITORS
Spironolactone
ALDOSTERONE
Competitive antagonist of the
aldosterone receptor
(myocardium, arterial walls, kidney)
Retention Na+
Retention H2O
Edema
Excretion K+
Arrhythmias
Excretion Mg2+
Collagen
deposition
Fibrosis
- myocardium
- vessels
RALES: All-Cause Mortality
1.00
Risk Reduction 30%
95% Cl (18%-40%)
P<0.001
0.95
0.90
0.85
0.80
Probability
of survival
Spironolactone
+ standard therapy
0.75
0.70
0.65
0.60
Standard therapy
(ACE inhibitor + loop
diuretic ± digoxin)
0.55
0.50
0.45
0
3
6
9 12 15 18 21 24 27 30 33 36
Months
Pitt B, Zannad F, Remme WJ, et al. N Engl J Med, 1999;341:709-717.
Relation Between LV Size
and Outcome in CHF
2-Year Mortality (%)
80
P = 0.004
60
40
20
0
>4 cm/m2
LV Index
M-mode echocardiography was performed on 382
patients with class III or IV HF (mean LVEF=20%)
<4 cm/m2
LV End-Diastolic Dimension
=
Estimated Body Surface Area
Lee TH et al. Am J Cardiol 1993
Cardiac Resynchronization Therapy

Cardiac resynchronization therapy (CRT) has
emerged as a promising new treatment for heart
failure patients with intraventricular conduction
delays or ventricular dysynchrony
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Studies of CRT have demonstrated
improvement in patient symptoms and exercise
capacity, quality of life, NYHA class(69% vs.
34% at 6 mnths).
Ventricular Dysynchrony
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Abnormal ventricular conduction resulting
in a mechanical delay
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Wide QRS (IVCD); typically LBBB
morphology
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Poor systolic function
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Impaired diastolic function
Abraham WT, et al. MIRACLE Trial Results; ACC 2001
Conclusions
In NYHA Class III and IV systolic heart
failure patients with intraventricular
conduction delays, CRT
is safe and well tolerated
 improves Quality of Life, functional class, and
exercise capacity
 improves cardiac structure and function
 improves heart failure composite response

Thank You