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