Pathophysiology

HEART FAILURE

Abdul Majid / Eka Roina M

Bagian Fisiologi
Fakultas Kedokteran USU , Medan
 Heart Failure
Inadequate pump function of the heart,
which leads to congestion resulting from
fluid in the lungs and peripheral tissues, is
a common end result of many cardiac
disease processes.
Ventricular dysfunction limits a patient's ability to
perform the routine activities of daily living
 Symptoms and signs of heart failure

1. forward failure:
symptoms result from inability of the heart to pump enough
blood to the periphery (from left heart), or to the lungs (from
the right heart)

a) forward failure of left heart:- muscle weakness, fatigue,

dyspepsia, oliguria....

general mechanism: tissue hypoperfusion

b) forward failure of right heart: - hypoperfusion of the

lungs disorders of gas
exchange
- decreased blood supply
to the left heart
2. backward failure:
symptoms result from inability of the heart to accept
the blood comming from periphery and from lungs

a. backward failure of left heart:

increased pulmonary capillary pressure dyspnoea
and tachypnoea, pulmonary edema (cardiac asthma)
arterial hypoxemia and hypercapnia....

b. backward failure of right heart:

increased pressure in systemic venous system
peripheral edemas, hepatomegaly, ascites nocturnal diuresis....
 Etiology
Inappropriate workloads placed on heart,
such as volume overload or pressure
overload
Restricted filling of the heart
Myocyte loss
Decreased myocyte contractility
 Compensatory Mechanisms

Frank-Starling Mechanism

Neurohormonal Activation

Ventricular Remodeling
 Hemodynamic Changes
Systolic Dysfunction
Isovolumic systolic
pressure curve of
the pressure-
volume
relationship is
shifted downward

This reduces stroke volume reduces

cardiac output
 Compensatory Mechanisms
Frank-Starling Mechanism
a. At rest, no HF
b. HF due to LV systolic dysfunction
c. Advanced HF
To maintain cardiac
output, heart respond
with three compensatory
mechanisms: First,
increased return of
blood to the heart
(preload) can lead to
increased contraction of
sarcomeres (Frank-
Starling relationship).

In the pressure-volume relationship, the heart

operates at a' instead of a, and stroke volume
increases,
 Compensatory Mechanisms
Neurohormonal Activation
Many different hormone systems are
involved in maintaining normal
cardiovascular homeostasis, including:
Sympathetic nervous system (SNS)
Renin-angiotensin-aldosterone system
(RAAS)
Vasopressin (a.k.a. antidiuretic hormone,
ADH)
Compensatory Mechanisms:
Sympathetic Nervous System
Decreased MAP

Sympathetic Nervous System

Contractility Tachycardia Vasoconstriction

MAP = (SV x HR) x TPR

Second, increased
release of
catecholamines can
increase cardiac
output by both
increasing the heart
rate and shifting the
systolic
isovolumetric curve
to the left
 Sympathetic Activation in Heart Failure
CNS sympathetic outflow

Cardiac sympathetic Sympathetic

activity activity to kidneys
+ peripheral vasculature

1- 2- 1- Activation
1- 1-
receptors receptors receptors of RAS

Myocardial toxicity Vasoconstriction

Increased arrhythmias Sodium retention

Disease progression
Packer. Progr Cardiovasc Dis. 1998;39(suppl I):39-52.
 Compensatory Mechanisms:
Renin-Angiotensin-Aldosterone (RAAS)
Angiotensinogen
Renin
Angiotensin I
Angiotensin
Converting
Enzyme Angiotensin II

AT I receptor

Vasoconstriction Vascular remodeling

Oxidative Stress LV remodeling

Cell Growth Proteinuria

 Compensatory Mechanisms:
Renin-Angiotensin-Aldosterone (RAAS)

Renin-Angiotensin-Aldosterone
( renal perfusion)

Salt-water retention Sympathetic

Vasoconstriction
Thirst augmentation

MAP = (SV x HR) x TPR

 Compensatory Mechanisms:
Neurohormonal Activation Vasopressin

Decreased systemic blood pressure

Central baroreceptors
-

Increased systemic Stimulation of hypothalamus,

blood pressure which produces vasopressin
for release by pituitary gland

Vasoconstriction Release of vasopressin by pituitary gland

 Compensatory Neurohormonal Stimulation: Summary
Decreased Cardiac Output

Sympathetic Renin-angiotensin Antidiuretic hormone

nervous system system (vasopressin)

Contractility Heart Vasoconstriction Circulating volume

rate
Anteriolar Venous

Maintain
blood
pressure Venous return
to heart
( preload)
Cardiac
+ output - Peripheral edema
and pulmonary
+ congestion
Stroke
volume
 Other Neurohormones
Natriuretic Peptides: Three known types
Atrial Natriuretic Peptide (ANP)
Predominantly found in the atria
Diuretic and vasodilatory properties
Brain Natriuretic Peptide (hBNP)
Predominantly found in the cardiac ventricles
Diuretic and vasodilatory properties
C-type Natriuretic Peptide (CNP)
Predominantly found in the central nervous system
Limited natriuretic and vasodilatory properties
 Pharmacological Actions of
hBNP
Hemodynamic
(balanced vasodilation)

veins

M
D
R I SS
S
arteries
S
K
R
G
L
coronary arteries
G G H
F
C S S
G
C
K V L
R
R
Neurohormonal
S P K M V
Q G S

aldosterone
norepinephrine
Renal
diuresis & natriuresis

Abraham WT and Schrier RW, 1994

 Endothelium-Derived
Vasoactive Substances
Produced by a thin lining of cells within the arteries and veins
called the endothelium
Endothelium-derived relaxing factors (EDRF) Vasodilators:
Nitric Oxide (NO)
Bradykinin
Prostacyclin
Endothelium-derived constricting factors (EDCF)
Vasoconstrictors:
Endothelin I
 Mediators of Heart Failure
Cytokines
Small protein molecules produced by a variety of
tissues and cells
Negative inotropes
Elevated levels associated with worse clinical
outcomes
Examples:
Tumor necrosis factor (TNF)-alpha
Interleukin 1-alpha
Interleukin-2
Interleukin-6
Interferon-alpha
Finally, cardiac muscle can
hypertrophy and
ventricular volume can
increase, which shifts the
diastolic curve to the right.

Although each of these compensatory

mechanisms can temporarily maintain cardiac
output, each is limited in its ability to do so, and
if the underlying reason for systolic dysfunction
remains untreated, the heart ultimately fails.
 Compensatory Mechanisms
Ventricular Remodeling
Alterations in the hearts size, shape, structure, and function brought about
by the chronic hemodynamic stresses experienced by the failing heart.

Curry CW, et al. Mechanical dyssynchrony in dilated cardiomyopathy with intraventricular conduction
delay as depicted by 3D tagged magnetic resonance imaging. Circulation 2000 Jan 4;101(1):E2.
 Vicious Cycle of Heart Failure

LV Dysfunction

Decreased cardiac output

Increased cardiac workload and
(increased preload and afterload) Decreased blood pressure

Increased cardiac output (via increased Frank-Starling Mechanism

contractility and heart rate) Remodeling
Increased blood pressure Neurohormonal activation
(via vasoconstriction
and increased blood volume)
Heart Failure
Hemodynamic effect

Pre Load Cardiac output

Reflex
Arteriolar
vasocons After Load
Sympathetic activity triction

Hypo Renal SVR

Na& Fluid Perfusion
retention

Neurohormonal hyperactivity
Renin, Angiotensin, Aldosterone, Vasopressin ,
ANP , BNP , Nor Epinephrine
 Left Ventricular Dysfunction
Systolic: Impaired contractility/ejection
Approximately two-thirds of heart failure patients have systolic
dysfunction1
Diastolic: Impaired filling/relaxation

30%
(EF > 40 %)
(EF < 40%)

70%

Diastolic Dysfunction
Systolic Dysfunction
1 Lilly, L. Pathophysiology of Heart Disease. Second Edition p 200
 Pathophysiology of diastolic heart failure

systolic heart failure = failure of ejecting function of the heart

diastolic heart failure = failure of filling the ventricles,

resistance to filling of ventricles

Diastolic failure is a widely recognized clinical entity

But, which of the cardiac cycle is real diastole ?

Definition of diastolic heart failure

It is pathophysiological process characterized by symptoms and signs

of congestive heart failure, which is caused by increased filling
resistance of ventricles and increased intraventricular diastolic
pressure

Primary diastolic heart failure

- no signs and symptoms of systolic dysfunction is present
- ! up to 40% of patients suffering from heart failure!

Secondary diastolic heart failure

- diastolic dysfunction is the consequence of primary
systolic dysfunction
Main causes and pathomechanisms of diastolic
heart failure

1. structural disorders passive chamber stiffness

a) intramyocardial
e.g. myocardial fibrosis, amyloidosis, hypertrophy,
myocardial ischemia...

b) extramyocardial e.g. constrictive pericarditis

2. functional disorders relaxation of chambers e. g. myocardial

ischemia, advanced hypertrophy of ventricles,
failing myocardium, asynchrony in heart
functions
Causes and mechanism participating on impaired
ventricular relaxation

a) physiological changes in chamber relaxation due to:

prolonged ventricular contraction
Relaxation of ventricles is not impaired !

b) pathological changes in chamber relaxation due to:

Impaired relaxation process

delayed relaxation (retarded)

incomplete (slowed) relaxation

 Diastolic Dysfunction
In diastolic dysfunction, the
position of the systolic
isovolumic curve remains
unchanged (contractility of
the myocytes is preserved).
The diastolic pressure-volume
curve is shifted to the left,
with an accompanying
increase in left ventricular
end-diastolic pressure and
symptoms of congestive
heart failure
 Patophysiology
Patients with isolated right ventricular failure
(pulmonary hypertension, cor pulmonale) can
have a mechanical reason for left ventricular
failure
When right ventricular pressure increases
relative to the left, the interventricular septum
can bow to the left and prevent efficient filling of
the left ventricle, which may lead to pulmonary
congestion.
Let it beat!