Heart Failure Pathophysiology.ppt [Read-Only]
[Pages:9]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
Types of Heart Failure
SHF
Diastolic
Pathophysiology Demographics 1? Cause
Impaired Contraction All ages
Coronary Artery Disease
Impaired filling > 60 years
Hypertension
Pressure Pressure Pressure
Systolic Versus Diastolic Failure
Systolic Dysfunction
Contractility
Normal
Diastolic Dysfunction
Capacitance
Volume
Volume
Volume
Systolic Versus Diastolic Failure
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
Decompensated Heart Failure
Heart Failure: Classifications
Right vs. Left Sided
Cardiac vs. Non-cardiac
Systolic vs. Diastolic
Dilated vs. Hypertrophic vs.
Restrictive
Heart Failure
Compensated vs. Decompensated
Acute vs. Chronic
Forward vs. Backward
High vs. Low Output
High vs. Low Output Failure
? Causes:
? Anemia ? Systemic arteriovenous fistulas ? Hyperthyroidism ? Beriberi heart disease ? Paget disease of bone ? Glomerulonephritis ? Polycythemia vera ? Carcinoid syndrome ? Obesity
Heart Failure: Classifications
Right vs. Left Sided
Cardiac vs. Non-cardiac
Systolic vs. Diastolic
Dilated vs. Hypertrophic vs.
Restrictive
Heart Failure
Compensated vs. Decompensated
Acute vs. Chronic
Forward vs. Backward
High vs. Low Output
Dilated vs. Hypertrophic vs. Restrictive
Type Dilated
Hypertrophic Restrictive
Definition
Sample Etiologies
Dilated left/both
Ischemic, idiopathic,
ventricle(s) with impaired familial, viral, alcoholic,
contraction
toxic, valvular
Left and/or right
Familial with autosomal
ventricular hypertrophy dominant inheritance
Restrictive filling and reduced diastolic filling of one/both ventricles, Normal/near normal systolic function
Idiopathic, amyloidosis, endomyocardial fibrosis
Dilated vs. Hypertrophic vs. Restrictive
Clinical Manifestations
Symptoms ? Reduced exercise tolerance ? Shortness of breath ? Congestion ? Fluid retention ? Difficulty in sleeping ? Weight loss
Diagnosis of heart failure
? Physical examination ? Chest X ray ? EKG ? Echocardiogram ? Blood tests: Na, BUN, Creatinine, BNP ? Exercise test ? MRI ? Cardiac catheterization
NYHA Classification
Class
I Mild II Mild
III Moderate
IV Severe
Patient Symptoms
? No limitation of physical activity ? No undue fatigue, palpitation or dyspnea
? Slight limitation of physical activity ? Comfortable at rest ? Less than ordinary activity results in fatigue,
palpitation, or dyspnea
? Marked limitation of physical activity ? Comfortable at rest ? Less than ordinary activity results in fatigue,
palpitation, or dyspnea
? Unable to carry out any physical activity without discomfort
? Symptoms of cardiac insufficiency at rest ? Physical activity causes increased discomfort
ACC/AHA Staging System
STAGE A High risk for developing HF STAGE B Asymptomatic LV dysfunction STAGE C Past or current symptoms of HF STAGE D End-stage HF
Hunt, et al. J Am Coll Cardiol. 2001; 38:2101-2113.
ACC/AHA Staging System
Stage
Patient Description
A High risk for
? Hypertension
developing heart failure ? Coronary artery disease
? Diabetes mellitus
? Family history of cardiomyopathy
B Asymptomatic heart failure
? Previous myocardial infarction ? Left ventricular systolic dysfunction
? Asymptomatic valvular disease
C Symptomatic heart failure
? Known structural heart disease ? Shortness of breath and fatigue
? Reduced exercise tolerance
D Refractory end-stage heart failure
? Marked symptoms at rest despite maximal medical therapy (e.g., those who are recurrently hospitalized or cannot be safely discharged from the hospital without specialized interventions)
Goals of Treatment
1. Identification and correction of underlying condition causing heart failure.
2. Elimination of acute precipitating cause of symptoms.
3. Modulation of neurohormonal response to prevent progression of disease.
4. Improve long term survival.
Treatment
Stage
Patient Treatment
A High risk for
? Hypertension
developing heart failure
???
OACspoptirimroinnaa,l rpAyhCaaErrmtienarhycibodilotiosgerisac,steshteartainpsy,
(OPT) b-blockers,
? aD-bi-abbleotceksemrse(lclaitruvsedilol) diabetic therapy
? Family history of cardiomyopathy
B Asymptomatic heart failure
?? OPPrTevious myocardial infarction
?? ICLDefitf vleefnt tvreicnutrliacruslayrst(oLlVi)cddyyssffuunnccttioionn(systolic) ? pAressyemntptomatic valvular disease
C Symptomatic heart failure
?? OKPnTown structural heart disease
?? ICSDhoifrtLnVesdsyosfubnrcetaiothn a(snydsftoatliicg)uperesent ?? CRReTd(uifcQedRSexweridceis,eLVtoEleFra3n5c%e)
D Refractory end-stage heart failure
?? OMPTarked symptoms at rest despite maximal
? InmterdmicitatlenthteIVraipnyot(reo.pge.,sthose who are recurrently ? IChoDsapsitaalbizreiddgoertocatnrannostpblaenstaafteiolyn discharged from ? CthReThospital without specialized interventions)
? Other devices (LVAD, pericardial restraint)
Targets of Treatment
Standard Pharmacological Therapy
? ACE inhibitors ? Angiotensin Receptor Blockers
? Beta Blcokers ? Diuretics
? Aldosterone Antagonists ? Statins
? Vasodilators ? Inotropes
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