Chapter 12: Heart Failure

Question 1

What is CHF?

Answer 1

Heart failure, often called congestive heart failure (CHF), is a common, usually progressive
condition with a poor prognosis.

Each year in the United States, CHF affects nearly 5 million individuals (approximately 2% of the population), necessitates over 1 million hospitalizations,
and is the primary or contributing cause of death of an estimated 300,000 people.

It is the
leading discharge diagnosis in patients over 65 years of age in the United States and has an
associated annual cost of $18 billion.

Question 2

When does CHF occurs?

Answer 2

CHF occurs when the heart is unable to pump blood at a rate sufficient to meet the metabolic
demands of the tissuesorcan do so only at an elevated filling pressure.

It can appear during
the end stage of many forms of chronic heart disease.

In this setting, it most often develops
insidiously due to the cumulative effects of chronic work overload(such as invalve disease or
hypertension)orischemic heart disease (e.g., following myocardial infarction with extensive
heart damage).

However, acute hemodynamic stresses, such as fluid overload, acute valvular dysfunction, or a large myocardial infarction, can cause CHF to appear suddenly

Question 3

What instances when CHF may occur suddenly?

Answer 3

However, acute hemodynamic stresses, such as fluid overload, acute valvular dysfunction, or a large myocardial infarction, can cause CHF to appear suddenly

Question 4

When cardiac function is impaired or the work load increases, several physiologic mechanisms
maintain arterial pressure and perfusion of vital organs. The most important of these are the
following:

Answer 4

• The Frank-Starling mechanism,
• Myocardial adaptations, including hypertrophy with or without cardiac chamber dilation .
• Activation of neurohumoral systems

Question 5

Discuss the Frank-Starling Mechanism.

Answer 5

The Frank-Starling mechanism, in which increased filling volumes dilate the heart and
thereby increase functional cross-bridge formation within the sarcomeres, enhancing
contractility

Question 6

What are your myocardial adaptations?

Answer 6

Myocardial adaptations, including hypertrophy with or without cardiac chamber dilation.

Question 7

What is ventricular remodeling?

Answer 7

The collective molecular, cellular, and structural changes that occur as a response to
injury or changesin loading conditions are called ventricular remodeling. [11]

Often
adaptive, especially in early stages, these changes can culminate in impaired cardiac function.

In many pathologic states, heart failure is preceded by cardiac hypertrophy, the compensatory response of the myocardium to increased mechanical work

Question 8

In many pathologic states, heart failure is preceded by __________, the compensatory response of the myocardium to increased mechanical work

Answer 8

cardiac hypertrophy

Question 9

When cardiac function is impaired or the work load increases, several physiologic mechanisms
maintain arterial pressure and perfusion of vital organs

Explain how Activation of neurohumoral systems can help maintain arterial pressure and perfusion.

Answer 9

Activation of neurohumoral systems , especially

• (1) release of norepinephrine by adrenergic cardiac nerves of the autonomic nervous system (which increases heart rate and augments myocardial contractility and vascular resistance);
• (2) activation of the renin-angiotensin-aldosterone system; and
• (3) release of atrial natriuretic peptide.

The latter two factors act to adjust filling volumes and pressures

Question 10

These adaptive mechanisms may be adequate to maintain normal cardiac output in the face of
heart disease, but their capacity to do so may ultimately be overwhelmed.

Moreover,
superimposed pathologic changes, such as ____________may cause further structural and functional disturbances.

Answer 10

• myocyte apoptosis,
• cytoskeletal alterations, and the
• deposition of extracellular matrix

Question 11

Most
frequently, heart failure results from ____________;

Answer 11

progressive deterioration of myocardial contractile function (systolic dysfunction)

this may be attributable to ischemic injury, pressure or volume overload due to valvular disease or hypertension, or dilated cardiomyopathy.

Sometimes, however,
failure results from an inability of the heart chamber to expand and fill sufficiently during diastole
(diastolic dysfunction), as can occur with massive left ventricular hypertrophy, myocardial
fibrosis, deposition of amyloid, or constrictive pericarditis (see below)

Question 12

What causes myocytes to increase in size (hypertrophy); cumulatively, this causes an
increase in the size and weight of the heart ( Fig. 12-1 ).

Answer 12

• Increased mechanical work due to pressure or
• volume overload (e.g., systemic hypertension oraortic stenosis), or
• trophic signals (e.g., those mediated through the activation of β-adrenergic receptors)

Question 13

Hypertrophy is dependent upon
_________, which enables the assembly of additional sarcomeres.

Answer 13

increased protein synthesis

Hypertrophic myocytes also contain increased numbers of mitochondria and have enlarged
nuclei.Thelatter alteration appears to be due to increases in DNA ploidy, which result from DNA replication in the absence of cell division.

Question 14

What is the reason for the enlarged nuclei in a hypertrophic myocites in the absence of cell division?

Answer 14

Hypertrophic myocytes also contain increased numbers of mitochondria and have enlarged
nuclei.

The latter alteration appears to be due to increases in DNA ploidy, which result from DNA replication in the absence of cell division

Question 15

The pattern of hypertrophy reflects the nature of
the stimulus.

T or F

Answer 15

True

Question 16

What is pressure-overload hypertrophy?

Answer 16

In response to increases in pressure (e.g., hypertension or aortic stenosis),
ventricles develop pressure-overload hypertrophy , which usually causes a concentric increase
in wall thickness.

In pressure overload, new sarcomeres are predominantly assembled in parallel to the long axes of cells, expanding the cross-sectional area of myocytes.

Question 17

What is volume-overload hypertrophy?

Answer 17

In contrast,
volume-overload hypertrophy is characterized by ventricular dilation.

This is because the new
sarcomeres assembled in response to volume overload are largely positioned in series with
existing sacromeres.

As a result, in dilation due to volume overload the wall thickness may be
increased, normal, or less than normal;thus,heart weight, rather than wall thickness, is the
best measure of hypertophy in volume overloaded hearts.

Question 18

Answer 18

FIGURE 12-1 Left ventricular hypertrophy.

• A, Pressure hypertrophy due to left ventricular outflow obstruction. The left ventricle is on the lower right in this apical four-chamber view of the heart.
• B, Left ventricular hypertrophy with and without dilation, viewed in transverse heart sections. Compared with a normal heart (center), the pressure-hypertrophied hearts (left and in A) have increased mass and a thick left ventricular wall, while the hypertrophied, dilated heart (right) has increased mass and a normal wall thickness.
• C, Normal myocardium.
• D, Hypertrophied myocardium. Note the increases in both cell size and nuclear size in the hypertrophied myocytes.

Question 19

Cardiac hypertrophy can be substantial in clinical heart disease.

Heart weights of two to three
times normal are common in patients with

Answer 19

• systemic hypertension,
• ischemic heart disease,
• aortic stenosis,
• mitral regurgitation, or dilated cardiomyopathy,

Question 20

Heart weights can be threefold to
fourfold greater than normal in those with aortic regurgitation or hypertrophic cardiomyopathyv

Answer 20

• aortic regurgitation or
• hypertrophic cardiomyopathyv

Question 21

Important changes at the tissue and cell level occur with cardiac hypertrophy

The increase in myocyte size is accompanied by a proportional increase in capillary numbers. .

T or F

Answer 21

FALSE

The increase in
myocyte size is not accompanied by a proportional increase in capillary numbers.

As a result,
the supply of oxygen and nutrients to the hypertrophied heart, particularly one undergoing
pressure overload hypertrophy, is more tenuous than in the normal heart.

At the same time,
oxygen consumption by the hypertrophied heart is elevated due to the increased workload that
drives the process.

Question 22

Hypertrophy is also often accompanied by deposition of fibrous tissue.

T or F

Answer 22

True

Question 23

Molecular changes in cardiac hypertrophy include the expression of immediate-early genes (e.g., c-fos, c-myc, c-jun,
and EGR1) ( Chapter 1 ). [13]

Answer 23

With prolonged hemodynamic overload, there may be a shift to a gene expression pattern resembling that seen during fetal cardiac development (including

• *selective expression of embryonic/fetal forms of β-myosin heavy chain, natriuretic peptides, and
  collagen) .**

Question 24

At a functional level, cardiac hypertrophy is associated with

Answer 24

heightened metabolic demands due
to increases in wall tension, heart rate, and contractility (inotropic state, or force of contraction),
all of which increase cardiac oxygen consumption

Question 25

As a result of these changes, the
hypertrophied heart is vulnerable ________________

Answer 25

to decompensation, which can evolve to cardiac failure and
eventually lead to death.

Question 26

Answer 26

The proposed sequence of initially beneficial, and later harmful,
events in response to increased cardiac work is summarized in Figure 12-2

FIGURE 12-2 Schematic representation of the causes and consequences of cardiac
hypertrophy.

Question 27

The molecular
and cellular changes in hypertrophied hearts that initially mediate enhanced function may
themselves contribute to the development of heart failure.

T or F

Answer 27

True

This can occur through

(1) abnormal myocardial metabolism, [15,[16
(2) alterations of intracellular handling of calcium ions,
(3) apoptosis of myocytes, and
(4) reprogramming of gene expression. [17,] [18]

The latterappears to occur in part through changes in expression of miRNAs, small noncoding RNAs that inhibit the expression of proteins at the level of mRNA stability or translation

Question 28

Cardiac hypertrophy is associated with down-regulation of _________

Answer 28

miR-208

Question 29

Cardiac hypertrophy is associated with upregulation of ___________

Answer 29

miR- 195

of interest, enforced over-expression of miR-195 can produce cardiac hypertrophy and
dilation in the mouse,whereasover-expression of miR-208is protective even in the setting of
pressure overload, suggesting a cause and effect relationship

Question 30

The degree of structural abnormality of the heart in CHF does not always reflect the level of
dysfunction, and the structural, biochemical, and molecular basis for myocardial contractile
failure can be obscure.

T or F

Answer 30

True

Indeed, it may be impossible from morphologic examination to
distinguish a damaged but functional heart from one that has failed

Question 31

At autopsy, the hearts of
patients with CHF are generally____________, but the extent of these changes is extremely variable.

Answer 31

heavy, dilated, and thin-walled and exhibit microscopic evidence
of hypertrophy

In myocardial infarction,
loss of pumping capacity due to myocyte death leads to work-related hypertrophy of the
surrounding viable myocardium.

In valvular heart disease, the increased pressure or volume
overloads the myocardium globally.

Question 32

Increased heart mass is correlated with excess cardiac mortality and morbidity; indeed,
cardiomegaly is an independent risk factor for sudden death.

T or F

Answer 32

T

Question 33

In contrast to pathologic
hypertrophy (which is often associated with contractile impairment), hypertrophy induced by regular strenuous exercise has varied effects on the heart depending on the type of exercise.

Aerobic exercise (e.g., long distance running) tends to be associated with______that may be accompanied by increases in capillary density (unlike other forms of
hypertrophy) and decreases in resting heart rate and blood pressure, effects that are all
beneficial.

These changes are sometimes referred to as physiologic hypertrophy.

Answer 33

volume-load
hypertrophy

Question 34

Static
exercise (e.g., weight lifting) is associated with ____________ and appears more likely to
be associated with deleterious changes

Answer 34

pressure hypertrophy

Question 35

Whatever its basis, CHF is characterized by _____________________

Answer 35

variable degrees of decreased cardiac output and
tissue perfusion (sometimes called forward failure), as well as pooling of blood in the venous
system (backward failure); the latter may cause pulmonary edema, peripheral edema, or both.
Thus, many of the significant clinical features and morphologic changes noted in CHF are
secondary to injuries induced by hypoxia and congestion in tissues distant from the heart.

Question 36

What is forward failure?

Answer 36

• *decreased cardiac output and**
• *tissue perfusion** (sometimes called forward failure),

Question 37

What is backward failure?

Answer 37

as well as pooling of blood in the venous
system (backward failure);

the latter may cause pulmonary edema, peripheral edema, or both.

Question 38

as well as pooling of blood in the venous
system (backward failure) may cause what?

Answer 38

pulmonary edema, peripheral edema, or both.

Question 39

The cardiovascular system is a closed circuit.

Thus, although left-sided and right-sided failure
can occur independently, failure of one side (particularly the left) often produces excessive
strain on the other, terminating in global heart failure.Despite this interdependency, it is easiest
to understand the pathology of heart failure by considering right- and left-sided heart failure
separately.

Question 40

LEFT-SIDED HEART FAILURE
Left-sided heart failure is most often caused by

Answer 40

• (1) ischemic heart disease,
• (2) hypertension,
• (3) aortic and mitral valvular diseases,
• and (4) myocardial diseases.

Question 41

The morphologic and
clinical effects of left-sided CHF primarily result from what?

Answer 41

• congestion of the pulmonary circulation,
• stasis of blood in the left-sided chambers, and hypoperfusion of tissues leading to organ dysfunction.

Question 42

The findings in the heart vary depending on the disease process;

gross structural abnormalities such as myocardial infarcts or a deformed, stenotic, or regurgitant valve may be present.

Except for failure caused by :

Answer 42

mitral valve stenosis or unusual restrictive
cardiomyopathies (described later), the left ventricle is usually hypertrophied and often
dilated, sometimes massively.

The microscopic changes are non-specific, consisting mainly
of myocyte hypertrophy and variable degrees of interstitial fibrosis. The impaired left
ventricular function usually causes dilation of the left atrium and increases the risk of atrial
fibrillation. This in turn results in stasis, particularly in the atrial appendage, which is a
common site of thrombus formation.

Question 43

What are the microscopic changes in the heart of LEFT-SIDED HEART FAILURE

Answer 43

The microscopic changes are:

• non-specific,
• consisting mainly of myocyte hypertrophy and
• variable degrees of interstitial fibrosis.

Question 44

The impaired left

ventricular function usually causes what?

Answer 44

dilation of the left atrium and increases the risk of atrial
fibrillation.

This in turn results in stasis, particularly in the atrial appendage, which is a
common site of thrombus formation.

Question 45

What is the appearance of the Lungs in Left-sided failure?

Answer 45

Pulmonary congestion and edema produce heavy, wet lungs, as described elsewhere ( Chapters 4 and 15 . Pulmonary changes include, in sequence from mildest to most severe, the following:

• (1) perivascular and interstitial edema, particularly in the interlobular septa, which is responsible for the characteristic Kerley B lines noted on chest roentgenogram;
• (2) progressive edematous widening of alveolar septa; and
• (3) accumulation of edema fluid in the alveolar spaces. Some red cells extravasate into the edema fluid within the alveolar spaces, where they are phagocytosed and digested by macrophages, which store the iron recovered from hemoglobin in the form of hemosiderin. These hemosiderin-laden macrophages are telltale signs of previous episodes of pulmonary edema and are often referred to as heart failure cells.

Question 46

What is the Kerley B lines?

Answer 46

perivascular and interstitial edema, particularly in the interlobular septa, which is responsible for the characteristic Kerley B lines noted on chest roentgenogram;

Question 47

What are heart failure cells?

Answer 47

accumulation of edema fluid in the alveolar spaces. Some red cells extravasate into the edema fluid within the alveolar spaces, where they are phagocytosed and digested by macrophages, which store the iron recovered from hemoglobin in the form of hemosiderin.

These hemosiderin-laden macrophages are telltale signs of previous episodes of pulmonary edema and are often referred to as heart failure cells.

Question 48

What are the clinical features of left-sided heart failures?

Answer 48

Clinically, in early left-sided heart failure symptoms may be quite subtle and are often related to
pulmonary congestion and edema.

• Cough and dyspnea (breathlessness), initially with exertion and later at rest, are two of the earliest complaints
• . As failure progresses, worsening pulmonary edema may lead to orthopnea (dyspnea when lying down that is relieved by standing), requiring

the patient to sleep in an upright position;

• or paroxysmal nocturnal dyspnea , a form of dyspnea usually occurring at night that is so severe that it induces a feeling of suffocation.

Particularly in the setting of atrial fibrillation, an arrhythmia characterized by uncoordinated, chaotic
contraction of the atrium, stasis greatly increases the risk of thrombosis and thomboembolic
stroke. [

Question 49

What are two earliest complaints in left side heart failure?

Answer 49

Cough and dyspnea (breathlessness), initially with exertion and later at rest, are two of the earliest complaints

Question 50

What is atrial fibrillation?

Answer 50

Particularly in
the setting of atrial fibrillation, an arrhythmia characterized by uncoordinated, chaotic
contraction of the atrium, stasis greatly increases the risk of thrombosis and thomboembolic stroke.

Question 51

What happens when cardiac output is decreased?

Answer 51

Decreased cardiac output causes a reduction in renal perfusion, which leads to the activation of
the renin-angiotensin-aldosterone system.

This in turn induces the retention of salt and water

• *and the expansion of the interstitial and intravascular fluid volume**s ( Chapters 4 and 11 ,
• *compensatory effects that can contribute to or exacerbate pulmonary edema.**

If the
hypoperfusion of the kidney becomes sufficiently severe, impaired excretion of nitrogenous
products may cause azotemia (called prerenal azotemia because of its vascular origin; Chapter
20 ).

In far-advanced CHF, cerebral hypoxia can give rise to hypoxic encephalopathy ( Chapter
28 ), with irritability, loss of attention span, and restlessness.

In end-stage CHF, this can even
progress to stupor and coma

Question 52

Left-sided heart failure can be divided on clinical grounds into :

Answer 52

systolic and diastolic failure.

Question 53

What is systolic failure?

Answer 53

Systolic failure is defined by insufficient cardiac output (pump failure), and can thus be caused
by any of the many disorders that damage or derange the contractile function of the left
ventricle.

Question 54

In diastolic failure, cardiac output is relatively preserved at rest, but the left ventricle is
abnormally stiff or otherwise restricted in its ability to relax during diastole.

T or F

Answer 54

True

As a result, the heart
is unable to increase its output in response to increases in the metabolic demands of peripheral
tissues (e.g., during exercise)

. Moreover, because the left ventricle cannot expand normally, any increase in filling pressure is immediately referred back to the pulmonary circulation, producing rapid onset pulmonary edema (sometimes referred to as flash pulmonary edema),
which may be severe.

Question 55

What is diastolic failure?

Answer 55

Diastolic failure predominantly occurs in patients over the age of 65 and
for unclear reasons is more common in women.

Question 56

What is the most underlying cause of diastolic failure?

Answer 56

Hypertension is the most common underlying
etiology.

Other risk factors include diabetes mellitus, obesity, and bilateral renal artery stenosis.
The reduction in the ability of the left ventricle to relax and fill may stem from myocardial fibrosis
(such as occurs in cardiomyopathies and ischemic heart disease), infiltrative disorders
associated with restrictive cardiomyopathies (e.g., cardiac amyloidosis), and restrictive
pericarditis.

Diastolic failure may also appear in elderly patients without any known predisposing
factors, possibly as an exaggeration of the normal stiffening of the heart with age, as discussed
previously.

Question 57

What is the most common cause of Right-side failure?

Answer 57

Most commonly, right-sided heart failure is caused by left-sided heart failure , as any increase
in pressure in the pulmonary circulation incidental to left-sided failure inevitably burdens the
right side of the heart.

Question 58

The causes of right-sided heart failure must then include all of those that
induce left-sided heart failure.

T or F

Answer 58

True

Question 59

When the pure Right-sided heart failure occurs?

Answer 59

Pure right-sided heart failure is infrequent and usually occurs in patients with any one of a variety of disorders affecting the lungs; hence, it is often referred to
as cor pulmonale

Question 60

Cor pulmonale is most commonly associate with ?

Answer 60

Cor pulmonale is most commonly associated with parenchymal diseases of
the lung, but can also arise secondary to disorders that affect the pulmonary vasculature (e.g.,
primary pulmonary hypertension ( Chapter 15 ), recurrent pulmonary thomboembolism (
Chapter 4 )), or that merely produce hypoxia (e.g., chronic sleep apnea, altitude sickness), with
its associated pulmonary vasoconstriction.

The common feature of these diverse disorders is

• *pulmonary hypertension** (discussed later), which results in hypertrophy and dilation of the right
• *side of the heart.**

In extreme cases, leftward bulging of the ventricular septum can cause left ventricular dysfunction.

Question 61

The major morphologic and clinical effects of right-sided heart failure differ from those of left-sided heart failure in that ______________

Answer 61

pulmonary congestion is minimal, whereas
engorgement of the systemic and portal venous systems may be pronounced

Question 62

LOOK AT BOOK for the last part of Right sided heart failure.