C h a p t e r 2 0
Heart Failure and Circulatory Shock
491
Myocardial hypertrophy and remodeling involve
a series of complex events at both the molecular and
cellular levels. The myocardium is composed of myo-
cytes, or muscle cells, and nonmyocytes. The myocytes
are the functional units of cardiac muscle. The nonmyo-
cytes include cardiac macrophages, fibroblasts, vascular
smooth muscle, and endothelial cells. These cells, which
are present in the interstitial space, remain capable of
an increase in cell number and provide support for the
myocytes. The nonmyocytes also determine many of
the inappropriate changes that occur during myocar-
dial hypertrophy. For example, uncontrolled fibroblast
growth is associated with increased synthesis of collagen
fibers, myocardial fibrosis, and ventricular wall stiffness.
Recent research has focused on understanding the type
of hypertrophy that develops in persons with heart fail-
ure. At the cellular level, cardiac muscle cells respond to
stimuli from stress placed on the ventricular wall by pres-
sure and volume overload by initiating several different
processes that lead to hypertrophy. These include stimuli
that produce a
symmetric hypertrophy
with a propor-
tionate increase in muscle length and width, as occurs in
athletes;
concentric hypertrophy
with an increase in wall
thickness, as occurs in hypertension; and
eccentric hyper-
trophy
with a disproportionate increase in muscle length,
as occurs in dilated cardiomyopathy
16
(Fig. 20-4). When
the primary stimulus for hypertrophy is
pressure over-
load,
the increase in wall stress leads to parallel replication
of myofibrils, thickening of the individual myocytes, and
concentric hypertrophy. Concentric hypertrophy may pre-
serve systolic function for a time, but eventually the work
performed by the ventricle exceeds the vascular reserve,
predisposing to ischemia. With
ventricular volume over-
load,
the increase in wall stress leads to replication of
myofibrils in series, elongation of the cardiac muscle cells,
and eccentric hypertrophy. Eccentric hypertrophy leads to
a decrease in ventricular wall thickness or thinning of the
wall with an increase in diastolic volume and wall tension.
Types of Heart Failure
Heart failure is commonly classified by the ejection frac-
tion (reduced or preserved) or as left-sided or right-sided
failure.
17
Heart failure with a reduced ejection fraction
(HFrEF) is defined as the inability of the ventricle to
eject an adequate cardiac output despite a normal blood
pressure with an EF
≤
40% .
1,18
Heart failure with a
preserved ejection fraction (HFpEF) is characterized by
a normal or normal EF (>50%) and abnormal diastolic
function.
5,18
Persons with a reduced or preserved ejec-
tion fraction may be symptomatic or asymptomatic. In
order to be diagnosed with heart failure, they must also
exhibit signs and symptoms, such as shortness of breath,
decreased exercise tolerance, and orthopnea (shortness
of breath when lying down).
Over the last decade, there has been growing rec-
ognition that approximately 50% of adult persons
with heart failure have normal or near normal ejection
fractions.
18–20
These people are as a group older, more
commonly female, and more frequently have systolic
hypertension (associated with large artery stiffness) than
those with a reduced ejection fraction. Most people with
HFpEF do not complain of symptoms at rest, but rather
with physical exercise. When present, the signs and
symptoms of heart failure are related to which ventricle
is dysfunctional: left or right.
Reduced versus Preserved Ejection Fraction
Heart failure can result frompump failure and an impaired
ability to eject blood at a rate commensurate with the met-
abolic needs of the tissues (systolic failure), or it can occur
because of resistance to filling of one or both ventricles
leading to symptoms of congestion (diastolic failure).
17
Reduced Ejection Fraction Heart Failure.
Heart fail-
ure with a reduced ejection fraction or systolic heart fail-
ure is defined as an EF of less than 40%.
21–23
It may result
from conditions that impair the contractile performance
of the heart (e.g., ischemic heart disease and cardiomy-
opathy), produce a volume overload (e.g., valvular insuf-
ficiency and anemia), or generate a pressure overload
(e.g., hypertension and valvular stenosis) on the heart.
Along with the decreased EF and cardiac output that
occurs with systolic failure, there is a resultant increase
in end-systolic and end-diastolic volumes, ventricular
dilation and wall tension, and a rise in ventricular end-
diastolic pressure.
17,22
This increased volume, in addition
to the normal venous return, leads to an increase in ven-
tricular preload. The rise in preload may represent a com-
pensatory response to maintain stroke volume through
the Frank-Starling mechanism despite a reduction in EF.
Increased preload, however, can also lead to an excessive
accumulation of blood in the atria and the pulmonary
venous system, which causes pulmonary congestion.
A
B
C
FIGURE 20-4.
Different types of myocardial hypertrophy.
(A)
Normal symmetric hypertrophy with
proportionate increases in myocardial wall thickness and length.
(B)
Concentric hypertrophy with
a disproportionate increase in wall thickness.
(C)
Eccentric hypertrophy with a disproportionate
decrease in wall thickness and ventricular dilation.
