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

................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download