C h a p t e r 2 0
Heart Failure and Circulatory Shock
487
that heart failure can occur even when the ejection frac-
tion is normal or preserved. Persons with symptoms or
below normal ejection fractions are classified as hav-
ing heart failure with a reduced ejection fraction, while
those with a normal or near-normal ejection fraction
are classified as having heart failure with a preserved
ejection fraction.
Pathophysiology of Heart Failure
In
heart failure,
the heart does not adequately pump
and/or fill with blood, which results in the inability to
meet the metabolic needs of the body.
1
The efficiency
of the heart as a pump is determined by the volume of
blood that it ejects each minute. The volume of blood
ejected is dependent upon the ability of the ventricles to
relax and fill.
5,6
The heart has the amazing capacity to
adjust its output to meet the varying needs of the body.
During sleep, the output declines, and during exercise, it
increases markedly. The ability of the heart to increase
its output during increased activity is called the
cardiac
reserve.
For example, competitive swimmers and long-
distance runners have large cardiac reserves. During
exercise, the cardiac output of these athletes rapidly
increases to as much as five to six times their resting
level.
6
In sharp contrast with healthy athletes, persons
with heart failure often use their cardiac reserve at rest.
For them, just climbing a flight of stairs or even walking
7
may cause shortness of breath because they exceed their
cardiac reserve.
Cardiac Performance and Output
The cardiac cycle consists of diastole and systole. During
diastole, normal filling of the ventricles increases the
volume of each to about 110 to 120 mL.
6
Then, as the
ventricles contract during systole, blood is ejected from
the heart, and the volume decreases by about 70 mL,
which is called the
stroke volume
. The fraction of the
end-diastolic volume that is ejected is called the
ejection
fraction
(usually about 60% in a healthy person).
6
Cardiac output, which is the major determinant
of cardiac performance, reflects how often the heart
beats each minute (heart rate) and how much blood it
ejects with each beat (stroke volume). Cardiac output
is expressed as the product of the heart rate and stroke
volume (i.e., cardiac output = heart rate × stroke vol-
ume). The heart rate is regulated by a balance between
the activity of the sympathetic nervous system, which
produces an increase in heart rate, and the parasympa-
thetic nervous system, which slows it down, whereas the
stroke volume is a function of preload, afterload, and
myocardial contractility.
5,6
Preload and Afterload.
The ability of the heart to eject
blood that has returned to the ventricles during diastole
is determined largely by the loading conditions, or what
are called the
preload
and
afterload.
Preload
reflects the volume of blood that stretches
the ventricle at the end of diastole, just before the onset
of systole. It is determined by the venous return to the
heart. Also known as the
end-diastolic volume,
preload
increases the length of the myocardial muscle fibers.
Within limits, as preload increases, the stroke volume
increases in accord with the Frank-Starling mechanism.
6
Afterload
represents the force that the contracting
heart muscle must generate to eject blood from the filled
ventricles. The main components of afterload are the
systemic (peripheral) vascular resistance and ventricular
wall tension. When the systemic vascular resistance is
elevated, as with arterial hypertension, an increased left
intraventricular pressure must be generated to first open
the aortic valve and then to eject blood out of the ven-
tricle and into the systemic circulation. This increased
pressure equates to an increase in ventricular wall stress
or tension.
6
Myocardial Contractility
Myocardial contractility, also known as
inotropy,
refers
to the contractile performance of the heart, or the ability
of the contractile elements (actin and myosin filaments)
of the heart muscle to interact and shorten against
a load
5,6,8
(see Chapter 1, Fig. 1-18). Contractility
increases cardiac output independent of preload and
afterload. The interaction between the actin and myosin
filaments during cardiac muscle contraction (i.e., cross-
bridge attachment and detachment) requires the use of
energy supplied by the breakdown of adenosine triphos-
phate (ATP) and the presence of calcium ions (Ca
++
).
8
As with skeletal muscle, calcium is released from
the sarcoplasmic reticulum of cardiac muscle during an
action potential (Fig. 20-1). This calcium, in turn, dif-
fuses into the myofibrils and catalyzes the chemical reac-
tions that promote the sliding of the actin and myosin
filaments along one another to produce muscle shorten-
ing. In addition to the calcium released from the sarco-
plasmic reticulum at the time of an action potential, a
large quantity of extracellular calcium diffuses into the
sarcoplasm through voltage-dependent L-type calcium
channels located in the T tubules and myocardial cell
membrane.Without the extra calcium that enters through
the L-type calcium channels, the strength of the cardiac
contraction would be considerably weaker. Opening of
the L-type calcium channels is facilitated by the second
messenger cyclic adenosine monophosphate (cAMP), the
formation of which is coupled to
β
-adrenergic receptors.
The catecholamines (norepinephrine and epinephrine)
exert their inotropic effects by binding to these adrener-
gic receptors. The L-type calcium channel also contains
several other types of receptors. Blockade of L-type cal-
cium channels by drugs that bind to these receptors (i.e.,
calcium channel-blocking drugs) results in a selective
reduction in cardiac contractility.
9
Another mechanism that can modulate inotropy is the
increased activity of the sodium ion (Na
+
)/Ca
++
exchange
pump and the ATPase-dependent Ca
++
pump in the
myocardial cell membrane (see Fig. 20-1). These pumps
transport calcium out of the cell, thereby preventing
the cell from becoming overloaded with calcium. If cal-
cium efflux is inhibited, the rise in intracellular calcium
produces an increased inotropy. Digitalis and related
