Heart Failure Pathophysiology.ppt [Read-Only]

Outline

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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

¨C From "syn¡° meaning "together¡° and "dromos"

meaning "a running¡°.

¨C 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

?

?

?

?

?

?

?

?

?

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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

?¡ü 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, ¡ü 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

¡ü CNS sympathetic outflow

Norepinephrine

¡ü Vascular sympathetic activity

¡ü Cardiac sympathetic activity

¦Â1

Hypertrophy, apoptosis, ischemia,

arrhythmias, remodeling, fibrosis

Morbidity and Mortality

¦Â2

¦Á1

Myocyte hypertrophy

Myocyte injury

Increased arrhythmias

¡ü Renal sympathetic activity

¦Á1

Vasoconstriction

¦Â1

Activation

of RAS

¦Á1

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

¨C Myocardial Infarction

¨C Myocardial Ischemia

?

?

Myocarditis

Toxins

¨C Anthracycline

¨C Alcohol

¨C 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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