Heart Failure Pathophysiology.ppt [Read-Only]
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Pathophysiology:
Heart Failure
Mat Maurer, MD
Irving Assistant Professor of Medicine
Definitions and Classifications
Epidemiology
Muscle and Chamber Function
Pathophysiology
Heart Failure: Definitions
Heart Failure
? An inability of the heart to pump blood at a sufficient rate
to meet the metabolic demands of the body (e.g. oxygen
and cell nutrients) at rest and during effort or to do so
only if the cardiac filling pressures are abnormally high.
? A complex clinical syndrome characterized by
abnormalities in cardiac function and neurohormonal
regulation, which are accompanied by effort intolerance,
fluid retention and a reduced longevity
? 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.
? Not a disease
? A syndrome
每 From "syn※ meaning "together※ and "dromos"
meaning "a running※.
每 A group of signs and symptoms that occur together
and characterize a particular abnormality.
? Diverse etiologies
? Several mechanisms
Etiologies
Ischemia
Diabetes
Hypertrophy
Hypertension
CAD
Arterial
Stiffness
Atrial
Fibrillation
Etiologies
Valvular Disease
Infiltrative
Disease
Pericardial
Disease
?
?
?
?
?
?
?
?
?
?
Ischemic cardiomyopathy
Valvular cardiomyopathy
Hypertensive cardiomyopathy.
Inflammatory cardiomyopathy
Metabolic cardiomyopathy
General system disease
Muscular dystrophies.
Neuromuscular disorders.
Sensitivity and toxic reactions.
Peripartal cardiomyopathy
Circulation. 1996;93:841-842
1
Heart Failure: Classifications
Forward vs.
Backward
High vs. Low
Output
? 3.5 million in 1991, 4.7 million
in 2000, estimated 10 million
in 2037
12
10
? Incidence: 550,000 new
cases/year
8
6
? Prevalence: 1% ages 50--59,
>10% over age 80
4
? More deaths from HF than
from all forms of cancer
combined
2
0
1991
2000
2037
? Most common cause for
hospitalization in age >65
From Muscle to Chamber
Cardiac Muscle Function
Afterload
Preload
Contractility
+norepinephrine
Tension (g)
Heart Failure Patients in the US
(Millions)
Epidemiology Heart Failure:
The Problem
d
b
a
?Lc
e
?La
c
Tension (g)
Acute vs. Chronic
Compensated vs.
Decompensated
Tension (g)
Heart Failure
f
b
g
a c
Muscle Length (mm)
Muscle Length (mm)
?The length of a cardiac
muscle fiber prior to the
onset of contraction.
?Frank Starling
?The against which a
cardiac muscle fiber
must shorten.
?Isotonic Contraction
e
a
Muscle Length (mm)
?The force of contraction
independent of preload
and afterload.
?Inotropic State
The Pressure Volume Loop
Systole
Dilated vs.
Hypertrophic vs.
Restrcitive
Systolic vs. Diastolic
Diastole
Cardiac vs.
Non-cardiac
Right vs. Left
Sided
Heart Failure Paradigms
2
The Pressure Volume Loop
Compliance/Stiffness vs Capacitance
Pes
d
oa
el
Pr
15
10
Capacitance =
volume at specified pressure
5
Slope = stiffness
= 1/compliance
0
-5
40
60
80
100 120 140
LV Volume (ml)
Volume
※Remodeling§
30
20
10
0
50
100
150
200
250
LV Volume (ml)
Afterload
Frank Starling Curves
Contractility
Hypotension
?EDV
?EDP
?Wall stress at end diastole
Normal
40
0
Cardiac Chamber Function
Preload
※Diastolic Dysfunciton§
50
20
ED
PV
R
ES
PV
R
EDPVR
20
LV Pressure (mmHg)
?
LV Pressure (mmHg)
Pressure
25
?Aortic Pressure
?Total peripheral resistance
?Arterial impedance
?Wall stress
Pulmonary
Congestion
?Pressure generated at
given volume.
?Inotropic State
Pathophysiology - PV Loop
Pathophyisiology of myocardial remodeling:
Transition from compensated hypertrophy to heart failure
Insult / Remodeling
Stimuli
?∥ Wall Stress
?Cytokines
?Neurohormones
?Oxidative stress
Increased Wall Stress
Myocyte Hypertrophy
Altered interstitial matrix
Fetal Gene Expression
Altered calcium handling
proteins
Myocyte Death
Ventricular
Enlargement
Diastolic
Dysfunction
Systolic
Dysfunction
3
Ventricular Remodeling
Laplace*s Law
Where P = ventricular pressure, r = ventricular chamber
radius and h = ventricular wall thickness
Neurohormonal Activation in
Heart Failure
Neurohormones in Heart Failure
Myocardial injury to the heart (CAD, HTN, CMP, valvular disease)
Fall in LV Performance
Myocardial Injury
Initial fall in LV performance, ∥ wall stress
Activation of RAAS and SNS
(endothelin, AVP, cytokines)
Activation of RAS and SNS
Remodeling and progressive
worsening of LV function
Fibrosis, apoptosis,
hypertrophy,
cellular/molecular
alterations,
myotoxicity
Peripheral vasoconstriction
Sodium retention
Hemodynamic alterations
Heart failure symptoms
Fatigue
Activity altered
Chest congestion
Edema
Shortness of breath
Morbidity and mortality
Arrhythmias
Pump failure
RAS, renin-angiotensin system; SNS, sympathetic nervous system.
Morbidity and Mortality
Peripheral Vasoconstriction
Sodium/Water Retention
Remodeling and
Progressive
Worsening of
LV Function
HF Symptoms
Shah M et al. Rev Cardiovasc Med. 2001;2(suppl 2):S2
Adrenergic Pathway in Heart
Failure Progression
Neurohormonal Activation in
Heart Failure
Angiotensin II
ANP
BNP
Myocardial Toxicity
Change in Gene Expression
∥ CNS sympathetic outflow
Norepinephrine
∥ Vascular sympathetic activity
∥ Cardiac sympathetic activity
汕1
Hypertrophy, apoptosis, ischemia,
arrhythmias, remodeling, fibrosis
Morbidity and Mortality
汕2
汐1
Myocyte hypertrophy
Myocyte injury
Increased arrhythmias
∥ Renal sympathetic activity
汐1
Vasoconstriction
汕1
Activation
of RAS
汐1
Sodium retention
Disease progression
4
Increased Blood Volume
Pathophysiology of Heart Failure
Aortic
Regurgitation
AI + Remodeling
AI + HF
Four Basic Mechanisms
Ventricular
Remodeling
1. Increased Blood Volume (Excessive Preload)
2. Increased Resistant to Blood Flow (Excessive
Afterload)
3. Decreased contractility
4. Decreased Filling
Etiologies
?Mitral Regurgitation
?Aortic Regurgitation
?Volume Overload
?Left to Right Shunts
?Chronic Kidney Disease
Increased Afterload
Hypertension
HTN + DD
Diastolic
Dysfunction
Etiologies
?Aortic Stenosis
?Aortic Coarctation
?Hypertension
Normal
BP (mm Hg)
HTN
HTN + DD
HTN +
Heart failure
159/122
170/129
206/159
61
51
54
65
Cardiac Output (L/min)
3.7
3.1
3.2
3.9
PCWP (mm Hg)
10
10
12
21
Decreased Filling
AI +
Remodeling
AI +
Heart failure
BP (mm Hg)
104/45/68
140/75/99
128/5078
85/35/54
SV (ml)
64
80
54
63
Cardiac Output (L/min)
3.8
3.0
2.1
2.6
PCWP (mm Hg)
10
10
10
20
MI + Remodeling
Na Retention
Vasoconstriction
Etiologies
? Ischemic Cardiomyopathy Parameter
每 Myocardial Infarction
每 Myocardial Ischemia
?
?
Myocarditis
Toxins
每 Anthracycline
每 Alcohol
每 Cocaine
MI + Heart Failure
Normal
MI
MI +
Remodeling
MI +
HF
80/50
BP (mm Hg)
124/81
68/46
68/45
SV (ml)
61
35
34
38
Cardiac Output (L/min)
3.7
2.1
2.0
2.3
PCWP (mm Hg)
10
16
18
33
Heart Failure: Classifications
HCM
Etiologies
? Mitral Stenosis
? Constriction
? Restrictive Cardiomypoathy
? Cardiac Tamponade
? Hypertrophic
Cardiomyopathy
? Infiltrative Cardiomyopathy
AI
Ventricular
Remodeling
124/81
Ventricular
Remodeling
Normal
Decreased Contractility
SV (ml)
Normal
Parameter
MI
HTN + DD + HF
Na Retention
Vasoconstriction
Parameter
Na Retention
Vasoconstriction
HCM + HF
Right vs. Left
Sided
Na Retention
Vasoconstriction
Parameter
Normal
HCM
HCM +
HF
BP (mm Hg)
131/87
124/81
112/74
SV (ml)
61
57
66
Cardiac Output (L/min)
3.7
3.4
4.0
PCWP (mm Hg)
10
10
27
Dilated vs.
Hypertrophic vs.
Restrcitive
Acute vs. Chronic
Cardiac vs.
Non-cardiac
Heart Failure
Forward vs.
Backward
Systolic vs. Diastolic
Compensated vs.
Decompensated
High vs. Low
Output
5
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