CHAPTER 9 • CARDIOVASCULAR INTEGRATION, ADAPTATION, AND PATHOPHYSIOLOGY
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or viral; alcohol-induced) or unknown origin
(idiopathic)
Infective or noninfective myocarditis (inflam-
mation of the myocardium)
Chronic arrhythmias
External
factors precipitating heart failure
include increased afterload (pressure load;
e.g., uncontrolled hypertension), increased
stroke volume (volume load; e.g., arterial-
venous shunts), and increased body demands
(high
output
failure;
e.g.,
thyrotoxicosis,
pregnancy).
Systolic versus Diastolic
Dysfunction
Heart failure can result from impaired ability
of the heart muscle to contract (systolic fail-
ure) or impaired filling of the heart (diastolic
failure). Systolic failure is caused by changes
in cellular signal transduction mechanisms
and
excitation-contraction
coupling
that
impair inotropy (see Chapter 3). Functionally,
this causes a downward shift in the Frank-
Starling
curve
(Fig.
9.8).
This
decreases
stroke volume and causes a compensatory rise
in preload (clinically assessed as increased
ventricular end-diastolic pressure or volume,
or increased pulmonary capillary wedge pres-
sure). Increased preload is an important com-
pensatory mechanism because it activates the
■ FIGURE 9.8 Effects of systolic failure on left
ventricular Frank-Starling curves. Systolic fail-
ure depresses the Frank-Starling curve, which
decreases stroke volume and leads to an increase
in ventricular preload
(LVEDP,
left ventricular end-
diastolic pressure). Point A, control point; point B,
systolic failure.
Frank-Starling mechanism to help maintain
stroke volume despite the loss of inotropy.
If preload did not undergo a compensatory
increase, the decline in stroke volume would
be even greater for a given loss of inotropy.
As systolic failure progresses, the ability of
the heart to compensate by the Frank-Starling
mechanism becomes exhausted as sarcomeres
stretch to their maximal length. Furthermore,
w ith chronic systolic failure, the ventricle
anatomically remodels by dilating. This is
achieved by new sarcomeres being added in
series to existing sarcomeres. Increased wall
circumference w ith the addition of new sar-
comere units prevents the individual sarcom-
eres from overstretching in the presence of
elevated filling pressures and volumes. The
dilated ventricle has increased compliance so
that it can accommodate large end-diastolic
volumes without excessive increases in end-
diastolic pressure (see Fig. 4.5).
The effects of a loss of inotropy on stroke
volume,
end-diastolic
volume,
and
end-
systolic volume can be depicted using ventric-
ular pressure-volume loops (Fig. 9.9, panel
A) (the concept of pressure-volume loops was
developed in Chapter 4; see Fig. 4.4). Systolic
failure decreases the slope of the end-systolic
pressure-volume relationship, w hich occurs
because of reduced inotropy. Because of this
change, at any given ventricular volume, less
pressure can be generated during systole, and
therefore, less volume can be ejected. This
leads to an increase in end-systolic volume.
The pressure-volume loop also shows that
the
end-diastolic
volume
increases
(com -
pensatory increase in preload). Ventricular
preload increases because as the heart loses
its ability to eject blood, more blood remains
in the ventricle at the end of ejection. This
results in the ventricle filling to a larger end-
diastolic volume
as
venous
return
enters
the
ventricle.
Increased
ventricular
filling
is enhanced by ventricular remodeling that
enlarges the chamber size (ventricular dila-
tion) and increases compliance. This permits
larger
end-diastolic
volumes w ith smaller
increases in end-diastolic pressure, although
this pressure can still rise to levels that lead
to blood backing up into the left atrium and
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