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HEART FAILURE

Heart failure generally is referred to as congestive heart

failure (CHF). CHF is the common end point for many

forms of cardiac disease and typically is a progressive condition that carries an extremely poor prognosis. In the

United States alone, nearly 5 million persons are affected,

resulting in more than 1 million hospitalizations and

300,000 deaths each year, with a fiancial burden in excess

of $18 billion. Most cases of heart failure are due to systolic

dysfunction—inadequate myocardial contractile function,

characteristically a consequence of ischemic heart disease

or hypertension. Alternatively, CHF also can result from

diastolic dysfunction—inability of the heart to adequately

relax and fil, such as in massive left ventricular hypertrophy, myocardial firosis, amyloid deposition, or constrictive pericarditis. Indeed, heart failure in elderly persons,

diabetic patients, and women may be more commonly

attributable to diastolic dysfunction. Various studies

suggest that 40–60% of cases of CHF may be due to diastolic dysfunction. Finally, heart failure also can be caused

by valve dysfunction (e.g., due to endocarditis) or can

occur in normal hearts suddenly burdened with an abnormal load (e.g., with flid or pressure overload).

CHF occurs when the heart cannot generate suffiient

output to meet the metabolic demands of the tissues—or

can only do so at higher-than-normal filing pressures; in

a minority of cases, heart failure can be a consequence of

greatly increased tissue demands, as in hyperthyroidism,

or poor oxygen carrying capacity as in anemia (high-output

failure). CHF onset can be abrupt, as in the setting of a large

myocardial infarct or acute valve dysfunction. In many

cases, however, CHF develops gradually and insidiously

owing to the cumulative effects of chronic work overload

or progressive loss of myocardium.

In CHF, the failing heart can no longer effiiently pump

the blood delivered to it by the venous circulation. The

result is an increased end-diastolic ventricular volume,

leading to increased end-diastolic pressures and, fially,

elevated venous pressures. Thus, inadequate cardiac

output—called forward failure—is almost always accompanied by increased congestion of the venous circulation—

that is, backward failure. As a consequence, although the root

problem in CHF typically is defiient cardiac function, virtually every other organ is eventually affected by some

combination of forward and backward failure.

The cardiovascular system attempts to compensate for

reduced myocardial contractility or increased hemodynamic burden through several homeostatic mechanisms:

• The Frank-Starling mechanism. Increased end-diastolic

filing volumes dilate the heart and cause increased

cardiac myofier stretching; these lengthened fiers contract more forcibly, thereby increasing cardiac output. If

the dilated ventricle is able to maintain cardiac output

by this means, the patient is said to be in compensated

heart failure. However, ventricular dilation comes at the

expense of increased wall tension and amplifis the

oxygen requirements of an already-compromised myocardium. With time, the failing muscle is no longer able

to propel suffiient blood to meet the needs of the body,

and the patient develops decompensated heart failure.

• Activation of neurohumoral systems:

 Release of the neurotransmitter norepinephrine by

the autonomic nervous system increases heart rate

and augments myocardial contractility and vascular

resistance.

 Activation of the renin-angiotensin-aldosterone

system spurs water and salt retention (augmenting

circulatory volume) and increases vascular tone.

 Release of atrial natriuretic peptide acts to balance the

renin-angiotensin-aldosterone system through diuresis and vascular smooth muscle relaxation.

• Myocardial structural changes, including augmented muscle

mass. Cardiac myocytes cannot proliferate, yet can

adapt to increased workloads by assembling increased

numbers of sarcomeres, a change that is accompanied

by myocyte enlargement (hypertrophy).

 In pressure overload states (e.g., hypertension or valvular stenosis), new sarcomeres tend to be added parallel to the long axis of the myocytes, adjacent to existing

sarcomeres. The growing muscle fier diameter thus results in concentric hypertrophy—the ventricular wall

thickness increases without an increase in the size of

the chamber.

 In volume overload states (e.g., valvular regurgitation

or shunts), the new sarcomeres are added in series

with existing sarcomeres, so that the muscle fier

length increases. Consequently, the ventricle tends

to dilate, and the resulting wall thickness can be

increased, normal, or decreased; thus, heart weight—

rather than wall thickness—is the best measure of

hypertrophy in volume-overloaded hearts.

Compensatory hypertrophy comes at a cost to the myocyte.

The oxygen requirements of hypertrophic myocardium are

amplifid owing to increased myocardial cell mass. Because

the myocardial capillary bed does not expand in step with

the increased myocardial oxygen demands, the myocardium becomes vulnerable to ischemic injury. Hypertrophy

also typically is associated with altered patterns of gene

expression reminiscent of the fetal myocytes, such as

changes in the dominant form of myosin heavy chain produced. Altered gene expression may contribute to changes

in myocyte function that lead to increases in heart rate and

force of contraction, both of which improve cardiac output,

but which also lead to higher cardiac oxygen consumption.

In the face of ischemia and chronic increases in workload,

other untoward changes also eventually supervene,

including myocyte apoptosis, cytoskeletal alterations, and

increased extracellular matrix (ECM) deposition.

Pathologic compensatory cardiac hypertrophy is correlated with increased mortality; indeed, cardiac hypertrophy is an independent risk factor for sudden cardiac death.

By contrast, the volume-loaded hypertrophy induced by

regular aerobic exercise (physiologic hypertrophy) typically is

accompanied by an increase in capillary density, with

decreased resting heart rate and blood pressure. These

physiologic adaptations reduce overall cardiovascular

morbidity and mortality. In comparison, static exercise

(e.g., weight lifting) is associated with pressure hypertrophy and may not have the same benefiial effects.

virtually every other organ is eventually affected by some

combination of forward and backward failure.

The cardiovascular system attempts to compensate for

reduced myocardial contractility or increased hemodynamic burden through several homeostatic mechanisms:

• The Frank-Starling mechanism. Increased end-diastolic

filing volumes dilate the heart and cause increased

cardiac myofier stretching; these lengthened fiers contract more forcibly, thereby increasing cardiac output. If

the dilated ventricle is able to maintain cardiac output

by this means, the patient is said to be in compensated

heart failure. However, ventricular dilation comes at the

expense of increased wall tension and amplifis the

oxygen requirements of an already-compromised myocardium. With time, the failing muscle is no longer able

to propel suffiient blood to meet the needs of the body,

and the patient develops decompensated heart failure.

• Activation of neurohumoral systems:

 Release of the neurotransmitter norepinephrine by

the autonomic nervous system increases heart rate

and augments myocardial contractility and vascular

resistance.

 Activation of the renin-angiotensin-aldosterone

system spurs water and salt retention (augmenting

circulatory volume) and increases vascular tone.

 Release of atrial natriuretic peptide acts to balance the

renin-angiotensin-aldosterone system through diuresis and vascular smooth muscle relaxation.

• Myocardial structural changes, including augmented muscle

mass. Cardiac myocytes cannot proliferate, yet can

adapt to increased workloads by assembling increased

numbers of sarcomeres, a change that is accompanied

by myocyte enlargement (hypertrophy).

 In pressure overload states (e.g., hypertension or valvular stenosis), new sarcomeres tend to be added parallel to the long axis of the myocytes, adjacent to existing

sarcomeres. The growing muscle fier diameter thus

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