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Heart FailureLast Updated: October 20,
|Synonyms and related keywords:
congestive heart failure, CHF, myocardial failure, circulatory
failure, renin-angiotensin-aldosterone system, RAAS, Frank-Starling
mechanism, myocardial hypertrophy, cardiac chamber dilatation,
neurohumoral systems, adrenergic cardiac nerves, ischemic
cardiomyopathy, Chagas disease, hypercapnic respiratory acidosis,
ventricular tachycardia, ventricular fibrillation, ventricular
arrhythmias, hypertension, diabetes, breathlessness, exertional
dyspnea, orthopnea, paroxysmal nocturnal dyspnea, dyspnea at rest,
acute pulmonary edema, intraaortic balloon pumping, IABP,
ventricular assist devices, biventricular pacing, cardiac
resynchronization, cardiac transplantation, heart transplantation
||Section 1 of 10
E Zevitz, MD, Clinical Assistant Professor, Department
of Medicine, Finch University of
Health Science, Chicago Medical School
|Michael E Zevitz, MD, is a member of the following medical
societies: American College of
Cardiology, American College
of Physicians, American
Medical Association, and Michigan State Medical Society
|Editor(s): George A Stouffer, III, MD, Interim
Director, Cardiac Catheterization Laboratory, Associate Professor,
Department of Medicine, Division of Cardiology, University of North
Carolina Medical Center, Chapel Hill; Francisco Talavera,
PharmD, PhD, Senior Pharmacy Editor, Pharmacy, eMedicine;
Marschall S Runge, MD, PhD, Chairman, Marion
Covington Distinguished Professor of Medicine, Department of
Medicine, University of North Carolina at Chapel Hill; Amer
Suleman, MD, Consultant in Electrophysiology and
Cardiovascular Medicine, Department of Internal Medicine, Division
of Cardiology, Medical Center of Plano; and Leonard Ganz,
MD, Director of Cardiac Electrophysiology, Associate
Professor, Department of Medicine, Division of Cardiology,
Cardiovascular Institute, University of Pittsburgh
||Section 2 of 10 |
failure is the pathophysiologic state in which the heart, via an
abnormality of cardiac function (detectable or not), fails to pump blood
at a rate commensurate with the requirements of the metabolizing tissues
and/or pumps only from an abnormally elevated diastolic filling pressure.
Heart failure may be caused by myocardial failure but may also occur in
the presence of near-normal cardiac function under conditions of high
demand. Heart failure always causes circulatory failure, but the converse
is not necessarily the case because various noncardiac conditions (eg,
hypovolemic shock, septic shock) can produce circulatory failure in the
presence of normal, modestly impaired, or even supranormal cardiac
In terms of incidence, prevalence, morbidity, and mortality, the
epidemiologic magnitude of congestive heart failure (CHF) is staggering.
In the United States, the estimated annual cost of heart failure is $60
billion; the estimated annual cost of inpatient care of patients with CHF
is $23 billion. Approximately 1 million US hospital admissions per year
are attributable to a primary diagnosis of acutely decompensated heart
Pathophysiology: Inadequate adaptation
of the cardiac myocytes to increased wall stress in order to maintain
adequate cardiac output following myocardial injury (whether of acute
onset or over several months to years, whether a primary disturbance in
myocardial contractility or an excessive hemodynamic burden placed on the
ventricle, or both), is the inciting event in CHF.
Most important among these adaptations are the (1) Frank-Starling
mechanism, in which an increased preload helps to sustain cardiac
performance; (2) myocardial hypertrophy with or without cardiac chamber
dilatation, in which the mass of contractile tissue is augmented; and (3)
activation of neurohumoral systems, especially the release of
norepinephrine (NE) by adrenergic cardiac nerves, which augments
myocardial contractility and the activation of the
renin-angiotensin-aldosterone system (RAAS) and other neurohumoral
adjustments that act to maintain arterial pressure and perfusion of vital
organs. In acute heart failure, the finite adaptive mechanisms that may be
adequate to maintain the overall contractile performance of the heart at
relatively normal levels become maladaptive when trying to sustain
adequate cardiac performance.
The primary myocardial response to chronic increased wall stress
includes myocyte hypertrophy and remodeling, usually of the eccentric
type. The reduction of cardiac output following myocardial injury sets
into motion a cascade of hemodynamic and neurohormonal derangements that
provoke activation of neuroendocrine systems, most notably the
above-mentioned adrenergic systems and RAAS. The release of epinephrine
(E) and NE, along with the vasoactive substances endothelin-1 (ET-1) and
vasopressin (V), causes vasoconstriction, which increases afterload, and,
via an increase in cyclic adenosine monophosphate (cAMP), causes an
increase in cytosolic calcium entry. The increased calcium entry into the
myocytes augments myocardial contractility and impairs myocardial
The calcium overload may also induce arrhythmias and lead to sudden
death. The increase in afterload and myocardial contractility (known as
inotropy) and the impairment in myocardial lusitropy lead to an increase
in myocardial energy expenditure and a further decrease in cardiac output.
The increase in myocardial energy expenditure leads to myocardial cell
death, resulting in heart failure and further reduction in cardiac output,
thus starting an accelerating cycle of further increased neurohumoral
stimulation and further adverse hemodynamic and myocardial responses as
In addition, the activation of the RAAS leads to salt and water
retention, resulting in increased preload and further increases in
myocardial energy expenditure. Increases in renin, mediated by decreased
stretch of the glomerular afferent arteriole, reduced delivery of chloride
to the macula densa, and increased beta1-adrenergic activity as a response
to decreased cardiac output, results in an increase in angiotensin II (Ang
II) levels and, in turn, aldosterone levels. This results in stimulation
of release of aldosterone. Ang II, along with ET-1, is crucial in
maintaining effective intravascular homeostasis mediated by
vasoconstriction and aldosterone-induced salt and water retention.
Some evidence indicates that local cardiac Ang II production, with a
resultant decrease in lusitropy, increase in inotropy, and increase in
afterload, leads to increased myocardial energy expenditure. In this
fashion, Ang II has similar actions to NE in CHF.
Ang II also mediates myocardial cellular hypertrophy and may promote
progressive loss of myocardial function. The neurohumoral factors above
lead to myocyte hypertrophy and interstitial fibrosis, resulting in
increased myocardial volume and increased myocardial mass, as well as
myocyte loss. The increase in myocardial volume results in myocyte
slippage, which also results in further increases in myocardial volume and
mass. These features, namely the increased myocardial volume and mass,
along with myocyte loss, are the hallmark of myocardial remodeling. This
remodeling process leads to early adaptive mechanisms, such as
augmentation of stroke volume (Starling mechanism) and decreased wall
stress (Laplace mechanism), and later, maladaptive mechanisms such as
increased myocardial oxygen demand, myocardial ischemia, impaired
contractility, and arrhythmogenesis.
As heart failure advances and/or becomes progressively decompensated,
there is a relative decline in the counterregulatory effects of endogenous
vasodilators, including nitric oxide (NO), prostaglandins (PGs),
bradykinin (BK), atrial natriuretic peptide (ANP), and B-type natriuretic
peptide (BNP). This occurs simultaneously with the increase in
vasoconstrictor substances from the RAAS and adrenergic systems. This
fosters further increases in vasoconstriction and thus preload and
afterload, leading to cellular proliferation, adverse myocardial
remodeling, and antinatriuresis with total body fluid excess and worsening
Both systolic and diastolic heart failure result in a decrease in
stroke volume. This leads to activation of peripheral and central
baroreflexes and chemoreflexes that are capable of eliciting marked
increases in sympathetic nerve traffic. While there are commonalities in
the neurohormonal responses to decreased stroke volume, the
neurohormone-mediated events that follow have been most clearly elucidated
for individuals with systolic heart failure. The ensuing elevation in
plasma NE directly correlates with the degree of cardiac dysfunction and
has significant prognostic implications. NE, while being directly toxic to
cardiac myocytes, is also responsible for a variety of signal-transduction
abnormalities, such as down-regulation of beta1-adrenergic receptors,
uncoupling of beta2-adrenergic receptors, and increased activity of
inhibitory G-protein. Changes in beta1-adrenergic receptors result in
overexpression and promote myocardial hypertrophy.
ANP and BNP are endogenously generated peptides activated in response
to atrial and ventricular volume/pressure expansion. ANP and BNP are
released from the atria and ventricles, respectively, and both promote
vasodilation and natriuresis. Their hemodynamic effects are mediated by
decreases in ventricular filling pressures, owing to reductions in cardiac
preload and afterload. BNP, in particular, produces selective afferent
arteriolar vasodilation and inhibits sodium reabsorption in the proximal
convoluted tubule. BNP inhibits renin and aldosterone release and,
possibly, adrenergic activation as well. Both ANP and BNP are elevated in
chronic heart failure. BNP, in particular, has potentially important
diagnostic, therapeutic, and prognostic implications.
Other vasoactive systems that play a role in the pathogenesis of CHF
include the ET receptor system, adenosine receptor system, V, and tumor
necrosis factor-alpha (TNF-alpha). ET, a substance produced by the
vascular endothelium, may contribute to the regulation of myocardial
function, vascular tone, and peripheral resistance in CHF. Elevated levels
of ET-1 closely correlate with the severity of heart failure. ET-1 is a
potent vasoconstrictor and has exaggerated vasoconstrictor effects in the
renal vasculature, reducing renal plasma blood flow, glomerular filtration
rate (GFR), and sodium excretion. TNF-alpha has been implicated in
response to various infectious and inflammatory conditions. Elevations in
TNF-alpha levels have been consistently observed in CHF and seem to
correlate with the degree of myocardial dysfunction. Experimental studies
suggest that local production of TNF-alpha may have toxic effects on the
myocardium, thus worsening myocardial systolic and diastolic function.
Thus, in individuals with systolic dysfunction, the neurohormonal
responses to decreased stroke volume result in temporary improvement in
systolic blood pressure and tissue perfusion. However, in all
circumstances, the existing data support the notion that these
neurohormonal responses accelerate the downward spiral of myocardial
dysfunction in the long term.
In diastolic heart failure, the same pathophysiologic processes to
decreased cardiac output that occur in systolic heart failure also occur,
but they do so in response to a different set of hemodynamic and
circulatory environmental factors that depress cardiac output.
In diastolic heart failure, altered relaxation of the ventricle (due to
delayed calcium uptake by the myocyte sarcoplasmic reticulum and delayed
calcium efflux from the myocyte) occurs in response to an increase in
ventricular afterload (pressure overload). The impaired relaxation of the
ventricle leads to impaired diastolic filling of the left ventricle (LV).
An increase in LV chamber stiffness occurs secondary to any one of the
following 3 mechanisms or to a combination thereof: (1) a rise in filling
pressure (ie, movement of the ventricle up along its pressure-volume curve
to a steeper portion, as may occur in conditions such as volume overload
secondary to acute valvular regurgitation or acute LV failure due to
myocarditis); (2) a shift to a steeper ventricular pressure-volume curve,
occurring most commonly as a result of not only increased ventricular mass
and wall thickness, as observed in (a) aortic stenosis and (b)
long-standing hypertension, but also in (c) infiltrative disorders such as
amyloidosis, (d) endomyocardial fibrosis, and (e) myocardial ischemia; and
(3) a parallel upward displacement of the diastolic pressure-volume curve,
generally referred to as a decrease in ventricular distensibility, usually
caused by extrinsic compression of the ventricles.
Whereas volume overload, as observed in chronic aortic and/or mitral
valvular regurgitant disease, shifts the entire diastolic pressure-volume
curve to the right, indicating increased chamber stiffness, pressure
overload that leads to concentric LV hypertrophy (as occurs in aortic
stenosis, hypertension, and hypertrophic cardiomyopathy) shifts the
diastolic pressure-volume curve to the left along its volume axis so that
at any diastolic volume ventricular diastolic pressure is abnormally
elevated, although chamber stiffness may or may not be altered. Increases
in diastolic pressure lead to increased myocardial energy expenditure,
remodeling of the ventricle, increased myocardial oxygen demand,
myocardial ischemia, and eventual progression of the maladaptive
mechanisms of the heart that lead to decompensated heart failure.
- In the US: CHF is the fastest-growing clinical
cardiac disease entity in the United States, affecting 2% of the
population. Nearly 1 million hospital admissions for acute decompensated
CHF occur in the United States yearly, almost double the number seen 15
years ago. The rehospitalization rates during the 6 months following
discharge are as much as 50%. Nearly 2% of all hospital admissions in
the United States are for decompensated CHF, and heart failure is the
most frequent cause of hospitalization in patients older than 65 years.
The average duration of hospitalization is about 6 days. An estimated
$23 billion are spent on inpatient management of CHF every year, and
another $40 billion are spent in the outpatient setting on patients with
compensated or mildly decompensated heart failure every year. Despite
aggressive therapies, hospital admissions for CHF continue to increase,
reflecting the prevalence of this malady.
- Internationally: CHF is a worldwide problem, but
few accurate financial data are available. As discussed elsewhere, the
most common cause of CHF in industrialized countries is ischemic
cardiomyopathy. Other causes, including Chagas disease, assume a more
important role in underdeveloped countries than in the United States.
Mortality/Morbidity: Despite recent advances in the
management of patients with heart failure, morbidity and mortality rates
remain high, with an estimated 5-year mortality rate of 50%.
- Assigning figures for inpatient mortality rates is difficult because
the causes and the severity of heart failure vary considerably. The most
recent estimates of inpatient mortality rates indicate that death occurs
in up to 5-20% of patients.
- Hypoxemia that occurs in decompensated CHF, which may be severe, may
result in myocardial ischemia or infarction.
- Respiratory failure with hypercapnic respiratory acidosis may occur
in severe decompensated CHF, requiring mechanical ventilation if medical
therapy is delayed or unsuccessful. Endotracheal intubation and
mechanical ventilation are associated with their own risks, including
aspiration (during the intubation process), mucosal trauma (more common
with nasotracheal intubation than orotracheal intubation), and
- In patients with CHF, the risk of cardiac sudden death from
ventricular tachycardia (VT) or ventricular fibrillation is
considerable, and the degree of risk is correlated with the degree of
decompensation and the degree of LV dysfunction. Recognition of the role
of ventricular arrhythmias and advances in their treatment have resulted
in decreased mortality rates in individuals with CHF.
- Progressive renal insufficiency due to decreased renal blood flow
and GFR are common in patients with long-standing CHF.
- Liver dysfunction due to passive hepatic congestion is particularly
common in patients with right-sided CHF with elevated right ventricular
(RV) pressure that is transmitted back into the portal vein.
- Mild jaundice, mild abnormalities in coagulation, and derangements
in liver metabolism of medications, some of which are used in the
treatment of heart failure, may result from this liver dysfunction.
- Toxic levels of medications such as warfarin, theophylline,
phenytoin, and digoxin can result from delayed liver metabolic
clearance of these drugs in the presence of decompensated CHF, thereby
leading to potentially fatal bleeding, cardiac dysrhythmias, and
Race: The incidence and prevalence of CHF are higher
in African Americans, Hispanic persons, Native Americans, and recent
immigrants from nonindustrialized nations, Russia, and the former Soviet
- The higher prevalence of CHF in African Americans, Hispanic persons,
and Native Americans is directly related to the higher incidence and
prevalence of hypertension and diabetes. This problem is particularly
exacerbated by a lack of access to health care and to substandard
preventive health care of the most indigent of these and other groups;
many persons within these groups are without adequate health insurance
- The higher incidence and prevalence of CHF among recent immigrants
from nonindustrialized nations is largely due to a lack of prior
preventive health care and to a lack of treatment or to substandard
treatment for common conditions such as hypertension, diabetes,
rheumatic fever, and ischemic heart disease.
Sex: Men and women have equivalent incidence and
prevalence of CHF. CHF in women tends to occur later in life compared to
Age: The prevalence of CHF increases with age, being
most common in individuals older than 65 years. In the United States, CHF
is the most common reason for hospital admission in patients older than 65
years. Nonetheless, CHF can occur at any age, depending on the cause.
History: Breathlessness, a
cardinal sign of LV failure, may manifest with progressively increasing
severity as (1) exertional dyspnea, (2) orthopnea, (3) paroxysmal
nocturnal dyspnea, (4) dyspnea at rest, and (5) acute pulmonary edema. The
New York Heart Association (NYHA) Classification of Heart Failure (see Staging),
which varies slightly from the above categorization of CHF symptoms, is
widely used in practice and in clinical studies to quantify clinical
assessment of CHF.
- The principle difference between exertional dyspnea in subjects
who are healthy and exertional dyspnea in patients with heart failure
is the degree of activity necessary to induce the symptom. As heart
failure first develops, exertional dyspnea may simply appear to be an
aggravation of the breathlessness that occurs in healthy persons
- As LV failure advances, the intensity of exercise resulting in
breathlessness progressively declines; however, subjective exercise
capacity and objective measures of LV performance at rest in patients
with heart failure are not closely correlated. Exertional dyspnea, in
fact, may be absent in sedentary patients.
- This early symptom of CHF may be defined as dyspnea that develops
in the recumbent position and is relieved with elevation of the head
with pillows. As in the case of exertional dyspnea, the change in the
number of pillows required is important.
- In the recumbent position, decreased pooling of blood in the lower
extremities and abdomen occurs. Blood is displaced from the
extrathoracic to the thoracic compartment. The failing LV, operating
on the flat portion of the Starling curve, cannot accept and pump out
the extra volume of blood delivered to it without dilating. As a
result, pulmonary venous and capillary pressures rise further, causing
interstitial pulmonary edema, reduced pulmonary compliance, increased
airway resistance, and dyspnea.
- In contrast to paroxysmal nocturnal dyspnea, orthopnea occurs
rapidly, often within a minute or two of recumbency, and develops when
the patient is awake. Orthopnea may occur in any condition in which
the vital capacity is low. Marked ascites, whatever its etiology, is
an important cause of orthopnea. In advanced LV failure, orthopnea may
be so severe that the patient cannot lie down and must sleep sitting
up in a chair or slumped over a table.
- Cough, particularly during recumbency, may be an "orthopnea
equivalent." This nonproductive cough may be caused by pulmonary
congestion and is relieved by treatments for heart failure.
- Paroxysmal nocturnal dyspnea
- Attacks of paroxysmal nocturnal dyspnea usually occur at night.
This symptom of CHF is defined by a sudden awakening of the patient,
after a couple hours of sleep, with a feeling of severe anxiety,
breathlessness, and suffocation. The patient may bolt upright in bed
and gasp for breath. Bronchospasm increases ventilatory difficulty and
the work of breathing and is a common complicating factor of
paroxysmal nocturnal dyspnea. On chest auscultation, the bronchospasm
associated with a CHF exacerbation can be difficult to distinguish
from an acute asthma exacerbation, although other clues from the
cardiovascular examination should lead the examiner to the correct
diagnosis. Both types of bronchospasm can be present in the same
- In contrast to orthopnea, which may be relieved by immediately
sitting up in bed, attacks of paroxysmal nocturnal dyspnea may require
30 minutes or longer in this position for relief. Episodes of this may
be so frightening that the patient may be afraid to resume sleeping,
even after the symptoms have abated.
- Dyspnea at rest - Mechanisms of dyspnea in heart failure
- Decreased pulmonary function
- Decreased compliance
- Increased airway resistance
- Increased ventilatory drive
- Hypoxemia due to increased pulmonary capillary wedge pressure
- Ventilation/perfusion (V/Q) mismatching due to increased PCWP
and cardiac output
- Increased carbon dioxide production
- Respiratory muscle dysfunction
- Decreased respiratory muscle strength
- Decreased endurance
- These symptoms are often accompanied by a feeling of heaviness in
- Fatigue and weakness are generally related to poor perfusion of
the skeletal muscles in patients with a lowered cardiac output.
Although generally a constant feature of advanced CHF, episodic
fatigue and weakness are common in earlier stages.
- Nocturia may occur relatively early in the course of heart
failure. Recumbency reduces the deficit in cardiac output in relation
to oxygen demand; renal vasoconstriction diminishes and urine
formation increases. This may be troublesome for the patient with
heart failure because it may prevent the patient from obtaining
- Oliguria is a late finding in CHF and is found in patients with
markedly reduced cardiac output from severely reduced LV
- Cerebral symptoms: Confusion, memory impairment, anxiety, headaches,
insomnia, bad dreams or nightmares, and rarely, psychosis with
disorientation, delirium, or hallucinations may occur in elderly
patients with advanced heart failure, particularly in those with
- Predominant right-sided heart failure
- Ascites, congestive hepatomegaly, and anasarca due to elevated
right-sided heart pressures transmitted backward into the portal vein
circulation may result in increased abdominal girth and epigastric and
right upper quadrant (RUQ) abdominal pain. Other gastrointestinal
symptoms, owing to congestion of the hepatic and gastrointestinal
venous circulation, include anorexia, bloating, nausea, and
constipation. In preterminal heart failure, inadequate bowel perfusion
can cause abdominal pain, distention, and bloody stools.
Distinguishing right-sided CHF from hepatic failure is often
- Dyspnea, prominent in LV failure, becomes less prominent in
isolated right-sided heart failure because of the absence of pulmonary
congestion. On the other hand, when cardiac output becomes markedly
reduced in patients with terminal right-sided heart failure (as may
occur in isolated RV infarction and in the late stages of primary
pulmonary hypertension and pulmonary thromboembolic disease), severe
dyspnea may occur as a consequence of the reduced cardiac output, poor
perfusion of respiratory muscles, hypoxemia, and metabolic
- General appearance
- Patients with mild heart failure appear to be in no distress after
a few minutes of rest, but they may be obviously dyspneic during and
immediately after moderate activity. Patients with LV failure may be
dyspneic when lying flat without elevation of the head for more than a
few minutes. Those with severe heart failure appear anxious and may
exhibit signs of air hunger in this position.
- Patients with recent onset of heart failure are generally well
nourished, but those with chronic severe heart failure are often
malnourished and sometimes even cachectic.
- Chronic marked elevation of systemic venous pressure may produce
exophthalmos and severe tricuspid regurgitation and may lead to
visible pulsation of the eyes and of the neck veins.
- Central cyanosis, icterus, and malar flush may be evident in
patients with severe heart failure.
- In mild or moderate heart failure, stroke volume is normal at
rest; in severe heart failure, it is reduced, as reflected by a
diminished pulse pressure and a dusky discoloration of the skin.
- With very severe heart failure, particularly if cardiac output has
declined acutely, systolic arterial pressure may be reduced. The pulse
may be weak, rapid, and thready; the proportional pulse pressure
(pulse pressure/systolic pressure) may be markedly reduced. The
proportional pulse pressure correlates reasonably well with cardiac
output. In one study, when pulse pressure was less than 25%, it
usually reflected a cardiac index of less than 2.2
- Evidence of increased adrenergic activity
- Increased adrenergic activity is manifested by tachycardia,
diaphoresis, pallor, peripheral cyanosis with pallor and coldness of
the extremities, and obvious distention of the peripheral veins
secondary to venoconstriction.
- Diastolic arterial pressure may be slightly
- Pulmonary rales
- Rales heard over the lung bases are characteristic of CHF of at
least moderate severity. With acute pulmonary edema, rales are
frequently accompanied by wheezing and expectoration of frothy,
- The absence of rales, however, certainly does not exclude
elevation of pulmonary capillary pressure due to LV
- Systemic venous hypertension: This is manifested by jugular venous
distention. Normally, jugular venous pressure declines with respiration;
however, it increases in patients with heart failure, a finding known as
the Kussmaul sign (also found in constrictive pericarditis).
- Hepatojugular reflux: This is found in patients with right-sided
heart failure and is helpful in differentiating hepatic enlargement due
to heart failure from that caused by other conditions.
- Although a cardinal manifestation of CHF, edema does not correlate
well with the level of systemic venous pressure. In patients with
chronic LV failure and low cardiac output, extracellular fluid volume
may be sufficiently expanded to cause edema in the presence of only
slight elevations in systemic venous pressure.
- Usually, a substantial gain of extracellular fluid volume (ie, a
minimum of 5 L in adults) must occur before peripheral edema is
- Edema, in the absence of dyspnea or other signs of LV or RV
failure, is not solely indicative of heart failure and can be observed
in many other conditions, including chronic venous insufficiency,
nephrotic syndrome, or other syndromes of hypoproteinemia or osmotic
- Hepatomegaly is prominent in patients with chronic right-sided
heart failure, but it may occur rapidly in acute heart failure.
- When occurring acutely, the liver is usually tender.
- In patients with considerable tricuspid regurgitation, a prominent
systolic pulsation of the liver, attributable to an enlarged right
atrial V wave, is often noted. A presystolic pulsation of the liver,
attributable to an enlarged right atrial A wave, can occur in
tricuspid stenosis, constrictive pericarditis, restrictive
cardiomyopathy involving the RV, and pulmonary hypertension (primary
- Hydrothorax (pleural effusion)
- Hydrothorax is most commonly observed in patients with
hypertension involving both systemic and pulmonary systems.
Hydrothorax is usually bilateral, although when unilateral, it is
usually confined to the right side of the chest.
- When hydrothorax develops, dyspnea usually intensifies because of
further reductions in vital capacity.
- This finding occurs in patients with increased pressure in the
hepatic veins and in the veins draining into the peritoneum.
- Ascites usually reflects long-standing systemic venous
- Protodiastolic (S3) gallop: This is the earliest cardiac
physical finding in decompensated heart failure in the absence of severe
mitral or tricuspid regurgitation or left-to-right shunts.
- A nonspecific finding, cardiomegaly nonetheless occurs in most
patients with chronic heart failure.
- Notable exceptions include heart failure from acute myocardial
infarction, constrictive pericarditis, restrictive cardiomyopathy,
valve or chordae tendineae rupture, or heart failure due to
tachyarrhythmias or bradyarrhythmias.
- Pulsus alternans
- Pulsus alternans occurs most commonly in heart failure due to
increased resistance to LV ejection, as occurs in hypertension, aortic
stenosis, coronary atherosclerosis, and dilated cardiomyopathy.
- It is usually associated with an S3 gallop, signifies
advanced myocardial disease, and often disappears with treatment of
- Accentuation of P2 heart sound, S3 gallop, and
- This accentuation is a cardinal sign of increased pulmonary artery
pressure. It disappears or improves after treatment of heart failure.
- Mitral and tricuspid regurgitation murmurs are often present in
patients with decompensated heart failure because of ventricular
dilatation. These murmurs often disappear or diminish when
compensation is restored. Note that correlation between the intensity
of the murmur of mitral regurgitation and its significance in patients
with CHF is poor. Severe mitral regurgitation may be accompanied by an
unimpressively soft murmur.
- The presence of an S3 gallop in adults is important,
pathologic, and often the most apparent finding on cardiac
auscultation in patients with significant CHF.
- Cardiac cachexia
- Cardiac cachexia is found in long-standing heart failure,
particularly of the RV, because of anorexia from hepatic and
intestinal congestion and sometimes because of digitalis toxicity.
Occasionally, impaired intestinal absorption of fat and (rarely)
protein-losing enteropathy occur.
- Patients with heart failure may also exhibit increased total
metabolism secondary to augmentation of myocardial oxygen consumption,
excessive work of breathing, low-grade fever, and elevated levels of
- Fever: Fever may be present in severe decompensated heart failure
because of cutaneous vasoconstriction and impairment of heat
Causes: From a clinical standpoint, it is useful to
classify the causes of heart failure into 3 broad categories: (1)
underlying causes, comprising structural abnormalities (congenital or
acquired) that affect the peripheral and coronary arterial circulation,
pericardium, myocardium, or cardiac valves, thus leading to the increased
hemodynamic burden or myocardial or coronary insufficiency responsible for
heart failure; (2) fundamental causes, comprising the biochemical and
physiological mechanisms, through which either an increased hemodynamic
burden or a reduction in oxygen delivery to the myocardium results in
impairment of myocardial contraction; and (3) precipitating causes,
including the specific causes or incidents that precipitate heart failure
in most episodes of heart failure.
Note that most patients who present with significant heart failure do
so because of an inability to provide adequate cardiac output in that
setting. This is often a combination of the causes listed above in the
setting of an abnormal myocardium. The list of causes responsible for
presentation of a patient with a CHF exacerbation is very long, and it is
important to search for the proximate cause in order to optimize
Overt heart failure may be precipitated by progression of the
underlying heart disease. A previously stable compensated patient may
develop heart failure that is clinically apparent for the first time when
the intrinsic process has advanced to a critical point, such as with
further narrowing of a stenotic aortic valve or mitral valve.
Alternatively, decompensation may occur as a result of failure or
exhaustion of the compensatory mechanisms but without any change in the
load on the heart in patients with persistent severe pressure or volume
- Precipitating causes of heart failure
- Inappropriate reduction of therapy: The most common cause of
decompensation in a previously compensated patient with heart failure
is inappropriate reduction in the intensity of treatment, whether
dietary sodium restriction, physical activity reduction, drug regimen
reduction, or, most commonly, a combination of these
- Tachyarrhythmias, most commonly atrial fibrillation
- Marked bradycardia
- Atrioventricular dissociation
- Abnormal intraventricular conduction
- Systemic infection or development of unrelated illness
- Systemic infection precipitates heart failure by increasing
total metabolism as a consequence of fever, discomfort, and cough,
which increases the hemodynamic burden on the heart.
- Septic shock, in particular, can precipitate heart failure by
the release of endotoxin-induced factors that can depress myocardial
- Pulmonary embolism: Patients with CHF, particularly when confined
to bed, are at high risk of developing pulmonary emboli, which can
increase the hemodynamic burden on the RV by further elevating RV
systolic pressure, possibly causing fever, tachypnea, and
- Physical, environmental, and emotional excesses: Intense,
prolonged physical exertion or severe fatigue, such as may result from
prolonged travel or emotional crises, or severe climate changes,
either to a hot, humid environment or to a bitterly cold environment,
are relatively common precipitants of cardiac
- Cardiac infection and inflammation
- Myocarditis or infective endocarditis may directly impair
myocardial function and exacerbate existing heart disease. The
anemia, fever, and tachycardia that frequently accompany these
processes are also deleterious.
- In the case of infective endocarditis, the additional valvular
damage that ensues may precipitate cardiac
- Excessive intake of water and/or sodium
- Administration of cardiac depressants or drugs that cause salt
- High-output states: Profound anemia, thyrotoxicosis, myxedema,
Paget disease of bone, Albright syndrome, multiple myeloma,
glomerulonephritis, cor pulmonale, polycythemia vera, obesity,
carcinoid syndrome, pregnancy, or nutritional deficiencies (eg,
thiamine deficiency, beriberi) can precipitate the clinical
presentation of CHF because of increased myocardial oxygen consumption
and demand beyond a critical level (ie, beyond the ability of the
underlying myocardial oxygen supply to meet these demands). In
particular, consider whether the patient has underlying coronary
artery disease or valvular heart disease.
- Development of a second form of heart disease
- Patients with one form of underlying heart disease that may be
well compensated can develop heart failure when a second form of
heart disease ensues.
- For example, a patient with chronic hypertension and
asymptomatic LV hypertrophy may be asymptomatic until a myocardial
infarction develops and precipitates heart
- Dominant systolic heart failure
- Ischemic myocardial disease, coronary artery disease
- Alcoholic cardiomyopathy
- Diabetic cardiomyopathy
- Cocaine cardiomyopathy
- Drug-induced cardiomyopathy (eg, doxorubicin)
- Idiopathic cardiomyopathy
- Peripartum cardiomyopathy
- Preterminal valvular heart disease
- Congenital heart disease with severe pulmonary hypertension
- Terminal ventricular septal defect or atrial septal
- Dominant diastolic heart failure
- Severe aortic stenosis
- Hypertrophic cardiomyopathy
- Restrictive cardiomyopathy
- Ischemic myocardial disease, coronary artery
- Acute heart failure
- Acute mitral or aortic regurgitation
- Rupture of valve leaflets or supporting structures
- Infective endocarditis with acute valve incompetence
- Myocardial infarction
- High-output heart failure
- Systemic arteriovenous fistulas
- Beriberi heart disease
- Paget disease of bone
- Albright syndrome (fibrous dysplasia)
- Multiple myeloma
- Cor pulmonale
- Polycythemia vera
- Carcinoid syndrome
||Section 4 of 10 |
Acute Respiratory Distress
Other Problems to be Considered:
CHF should be differentiated from pulmonary edema associated with
injury to the alveolar-capillary membrane caused by diverse etiologies
(ie, noncardiogenic pulmonary edema, adult respiratory distress syndrome
[ARDS]). Increased capillary permeability is observed in trauma,
hemorrhagic shock, sepsis, respiratory infections, administration of
various drugs, and ingestion of toxins such as heroin, cocaine, and toxic
Several features may differentiate cardiogenic heart failure
from noncardiogenic pulmonary edema. In CHF, a history of an acute cardiac
event or that of progressive symptoms of heart failure is usually present.
The physical examination reveals a low-flow state, S3 gallop,
elevated jugular venous distention, and crackles upon
Patients with noncardiogenic pulmonary edema have a
warm periphery, a bounding pulse, and an absence of S3 gallop
and jugular venous distention. Differentiation is often made based on PCWP
measurements from invasive hemodynamic monitoring. PCWP is generally more
than 18 mm Hg in CHF and is less than 18 mm Hg in noncardiogenic pulmonary
edema, but superimposition of chronic pulmonary vascular disease can make
this distinction more difficult to discern. With the advent of BNP level
testing, reliably differentiating cardiac causes of pulmonary congestion
from noncardiac causes is now possible.
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- CBC count: This study aids in the assessment of severe anemia, which
may cause or aggravate heart failure. Leukocytosis may signal underlying
infection. Otherwise, CBC counts are usually of little diagnostic
- Serum electrolyte values are generally within reference ranges in
patients with mild-to-moderate heart failure before treatment.
However, in severe heart failure, prolonged, rigid sodium restriction,
coupled with intensive diuretic therapy and the inability to excrete
water, may lead to dilutional hyponatremia, which occurs because of a
substantial expansion of extracellular fluid volume and a normal or
increased level of total body sodium.
- Potassium levels are usually within reference ranges, although the
prolonged administration of diuretics may result in hypokalemia.
Hyperkalemia may occur in patients with severe heart failure who show
marked reductions in GFR and inadequate delivery of sodium to the
distal tubular sodium-potassium exchange sites of the kidney,
particularly if they are receiving potassium-sparing diuretics and/or
- Renal function tests
- BUN and creatinine levels can be within reference ranges in
patients with mild-to-moderate heart failure and normal renal
function, although elevated BUN and BUN/creatinine ratios may also be
- Patients with severe heart failure, particularly those on large
doses of diuretics for long periods, may have elevated BUN and
creatinine levels indicative of renal insufficiency because of chronic
reductions of renal blood flow from reduced cardiac output. Diuretics
may aggravate renal insufficiency when these patients are
overmedicated with diuretics and become volume
- Liver function tests
- Congestive hepatomegaly and cardiac cirrhosis are often associated
with impaired hepatic function, which is characterized by abnormal
values of aspartate aminotransferase (AST), alanine aminotransferase
(ALT), lactic dehydrogenase (LDH), and other liver enzymes.
- Hyperbilirubinemia, secondary to an increase in both the directly
and indirectly reacting bilirubin, is common. In severe cases of acute
RV or LV failure, frank jaundice may occur.
- Acute hepatic venous congestion can result in severe jaundice,
with a bilirubin level as high as 15-20 mg/dL, elevation of AST to
more than 10 times the upper reference range limit, elevation of the
serum alkaline phosphatase level, and prolongation of the prothrombin
time. Both the clinical and the laboratory pictures may resemble viral
hepatitis, but the impairment of hepatic function is rapidly resolved
by successful treatment of heart failure. In patients with
long-standing heart failure, albumin synthesis may be impaired,
leading to hypoalbuminemia and intensifying the accumulation of fluid.
- Fulminant hepatic failure is an uncommon, late, and sometimes
terminal complication of cardiac cirrhosis.
- B-type natriuretic peptide
- BNP is a 32-amino acid polypeptide containing a 17-amino acid ring
structure common to all natriuretic peptides. Unlike ANP, whose major
storage sites are in both the atria and ventricles, the major source
of plasma BNP is the cardiac ventricles, suggesting that BNP may be a
more sensitive and specific indicator of ventricular disorders than
other natriuretic peptides. The release of BNP appears to be in direct
proportion to ventricular volume expansion and pressure overload. BNP
is an independent predictor of high LV end-diastolic pressure and is
more useful than ANP or NE levels for assessing mortality risk in
patients with CHF.
- BNP levels rise with age. Mean BNP levels are 26.2 +/- 1.8 pg/mL
in the group aged 55-64 years, 31.0 +/- 2.4 pg/mL for the group aged
65-74 years, and 63.7 +/- 6 pg/mL for the group aged 75 years and
older. Additionally, women without CHF tend to have somewhat higher
BNP levels than their male cohorts of the same age, with women 75
years and older having a mean BNP level of 76.5 +/- 3.5 pg/mL.
Although the reason is unknown, aging women possibly have stiffer
ventricles than age-matched men.
- BNP levels correlate closely with the NYHA Classification of Heart
Failure as well as the Goldman Activity Classification of Heart
- BNP levels of more than 100 pg/mL have better than a 95%
specificity and greater than a 98% sensitivity when comparing patients
without CHF to all patients with CHF. Even BNP levels of more than 80
pg/mL have greater than a 93% specificity and 98% sensitivity in the
diagnosis of heart failure. Furthermore, BNP levels, in several pilot
studies, had a strong correlation with the severity of illness and
were very reliable in differentiating CHF from pulmonary disease.
- BNP levels also correlate highly with the change in PCWP pressure.
It has been proposed that BNP levels may be a useful surrogate
indicator of PCWP, although this is not common in clinical practice.
BNP may help in tailoring treatment of the decompensated patient.
- In a pilot study, BNP levels correlated highly with clinical
outcomes. Patients with decreased BNP levels during their hospital
stay, along with decreases in NYHA classification, had good outcomes,
whereas patients whose hospital stay ended in death or readmission
within 30 days of discharge had only minimal decreases of BNP levels
or rising levels of BNP despite improvement or no change in their NYHA
classification. In addition, the last measured BNP level was the
single most reliable variable in predicting short-term outcomes in
patients with CHF.
- Chest radiographs are very helpful in distinguishing cardiogenic
pulmonary edema (CPE) from other pulmonary causes of severe
- Classic radiographic findings demonstrate cardiomegaly (in
patients with underlying CHF) and alveolar edema with pleural
effusions and bilateral infiltrates in a butterfly pattern. The other
signs are loss of sharp definition of pulmonary vasculature, haziness
of hilar shadows, and thickening of interlobular septa (Kerley B
- Chest radiographs in patients with abrupt onset are usually
helpful but can be limited because a delay of as long as 12 hours is
possible from the onset of dyspnea due to acute heart failure to the
development of classic abnormal findings on x-ray films.
- This is the easiest and least-expensive method of determining LV
function, both systolic and diastolic. Echocardiography is also the
easiest and least-expensive method of determining the presence of
valvular heart disease, LV wall thickness, chamber sizes, presence of
pericardial disease, and regional wall motion abnormalities that may
suggest ischemic coronary artery disease as the cause.
Echocardiography is very reliable in diagnosing the cause or causes of
- Transesophageal echocardiography is particularly useful in
patients who are on mechanical ventilation or morbidly obese and in
patients whose transthoracic echocardiogram was suboptimal in its
imaging. It is an easy and safe alternative to conventional
transthoracic echocardiography and provides superior imaging quality
compared to conventional transthoracic echocardiography.
- Radionuclide multiple gated acquisition scan
- Radionuclide multiple gated acquisition (MUGA) scan is a very
reliable imaging technique for determining global heart function. LV
ejection fraction, as determined by MUGA scanning, is often used for
serial assessment of LV function because of its
- However, this study is limited in its assessment of valvular heart
disease and pericardial disease.
- ABGs usually reveal mild hypoxemia in patients who have
mild-to-moderate heart failure. ABGs are more accurate than pulse
oximetry for measuring oxygen saturation. Patients with severe heart
failure may have signs and symptoms ranging from severe hypoxemia, or
even hypoxia, along with hypercapnia, to decreased vital capacity and
- ABGs help to assess the presence of hypercapnia, a potential early
marker for impending respiratory failure. Hypoxemia and hypocapnia
occur in stages 1 and 2 of pulmonary edema because of V/Q mismatch. In
stage 3 of pulmonary edema, right-to-left intrapulmonary shunt
develops secondary to alveolar flooding and further contributes to
hypoxemia. In more severe cases, hypercapnia and respiratory acidosis
are usually observed. The decision regarding intubation and use of
mechanical ventilation is frequently based on the presence of
hypercapnic respiratory failure with acidosis discovered on ABGs in
patients with fulminant pulmonary edema.
- Pulse oximetry is highly accurate at assessing the presence of
hypoxemia and, therefore, the severity of heart failure.
- Patients with mild-to-moderate heart failure show modest
reductions in oxygen saturation, whereas patients with severe heart
failure may have severe oxygen desaturation, even at rest.
- Patients with mild-to-moderate heart failure may have normal
oxygen saturations at rest, but they may exhibit marked reductions in
oxygen saturations during physical exertion or recumbency,
necessitating the use of continuous oxygen until compensation either
returns oxygen saturation to normal during exertion and recumbency or
on a permanent basis if oxygen desaturation during exertion and/or
recumbency exist during compensated severe heart failure.
- Pulse oximetry is useful for monitoring the patient’s response to
supplemental oxygen and other therapies.
- The presence of left atrial enlargement and LV hypertrophy is
sensitive (although nonspecific) for chronic LV dysfunction.
- ECG may suggest an acute tachyarrhythmia or bradyarrhythmia as the
cause of heart failure.
- ECG may aid in the diagnosis of acute myocardial ischemia or
infarction as the cause of heart failure or may suggest the likelihood
of prior myocardial infarction or presence of coronary artery disease
as the cause of heart failure.
- ECG is of limited help when an acute valvular abnormality or LV
systolic dysfunction is considered to be the cause of heart failure;
however, the presence of left bundle branch block (LBBB) on an ECG is
a strong marker for diminished LV systolic function.
- Right-sided heart catheterization
- PCWP can be measured by using a pulmonary arterial catheter
(Swan-Ganz catheter), and this helps differentiate cardiogenic causes
of decompensated heart failure from noncardiogenic causes such as
ARDS, which occurs secondary to injury to the alveolar-capillary
membrane rather than to alteration in Starling forces. A PCWP
exceeding 18 mm Hg in a patient not known to have chronically elevated
left atrial pressure is indicative of cardiogenic decompensated heart
failure. In patients with chronic pulmonary capillary hypertension,
capillary wedge pressures exceeding 30 mm Hg are generally required to
overcome the pumping capacity of the lymphatics and produce pulmonary
- Large V waves may sometimes be observed in the PCWP tracing with
acute mitral regurgitation because large volumes of blood regurgitate
into a poorly compliant left atrium. This raises pulmonary venous
pressure and causes acute pulmonary edema. The pulmonary artery
waveform appears falsely elevated because of the large V wave
reflected from the left atrium through the compliant pulmonary
vasculature. The Y descent of the waveform is quite rapid as the
overdistended left atrium quickly empties. Patients with long-standing
mitral regurgitation and left atrial enlargement may demonstrate much
less impressive V waves even in the setting of very significant mitral
- Cardiogenic shock is the result of a severe depression in
myocardial function. Although many definitions for cardiogenic shock
have been proposed, the following provides a useful guideline:
Cardiogenic shock is present when systolic blood pressure is less than
80 mm Hg, the cardiac index is less than 1.8 L/min/m2, and
the PCWP is greater than 18 mm Hg. This form of shock can occur from a
direct insult to the myocardium (eg, large acute myocardial
infarction, severe cardiomyopathy) or from a mechanical problem that
overwhelms the functional capacity of the myocardium (eg, acute severe
mitral regurgitation, acute ventricular septal defect). The prognosis
of patients with cardiogenic shock is poor, with in-hospital mortality
rates of 50-90%.
- Left-sided heart catheterization and coronary angiography
- Left-sided heart catheterization and coronary angiography should
be undertaken when the etiology of heart failure cannot be determined
by clinical or noninvasive imaging methods or when the etiology is
likely to be due to acute myocardial ischemia or myocardial
infarction. Coronary angiography is particularly helpful in patients
with LV systolic dysfunction and known or suspected coronary artery
disease in whom myocardial ischemia is thought to play a dominant role
in the reduction of LV systolic function and the worsening of heart
failure. As a general rule, most patients with clinically significant
CHF should undergo cardiac catheterization to exclude the reversible
causes listed above.
- Specific rationales for right- and left-sided heart
catheterization include the need to determine the etiologic
significance and severity of mitral and/or aortic valvular disease in
patients with heart failure in whom the cause-effect relationship of
valvular heart disease with regard to heart failure is unclear.
Furthermore, right- and left-sided heart catheterization should be
performed in patients in whom constrictive pericarditis is considered
a likely cause of heart failure.
- A classification of patients with heart disease based on the
relation between symptoms and the amount of effort required to provoke
them has been developed by the NYHA.
- Class I: No limitations. Ordinary physical activity does not cause
undue fatigue, dyspnea, or palpitations.
- Class II: Slight limitation of physical activity. Such patients
are comfortable at rest. Ordinary physical activity results in
fatigue, palpitations, dyspnea, or angina.
- Class III: Marked limitation of physical activity. Although
patients are comfortable at rest, less-than-ordinary activity leads to
fatigue, dyspnea, palpitations, or angina.
- Class IV: Symptomatic at rest. Symptoms of CHF are present at
rest; discomfort increases with any physical activity.
- The Goldman Activity Classification of Heart Failure is based on
estimated metabolic cost of various activities, and classes correlate to
- Class I: Patients can perform to completion any activity up to 7
metabolic equivalents (METS).
- Class II: Patients can perform to completion any activity up to 5
METS of activity but cannot perform to completion any activities equal
to or more than 7 METS.
- Class III: Patients can perform to completion any activity up to 2
METS of activity but cannot perform to completion any activities equal
to or more than 5 METS.
- Class IV: Patients cannot perform to completion activities equal
to or more than 2 METS.
||Section 6 of 10 |
Medical Care: Medical therapy of heart failure focuses on 3 main goals: (1)
preload reduction, (2) reduction of systemic vascular resistance
(afterload reduction), and (3) inhibition of both the RAAS systems and
vasoconstrictor neurohumoral factors produced by the sympathetic nervous
system in patients with heart failure. The first 2 goals provide
symptomatic relief. While reducing symptoms, inhibition of the RAAS and
neurohumoral factors also results in significant reductions in morbidity
and mortality rates.
Preload reduction results in decreased pulmonary capillary hydrostatic
pressure and reduction of fluid transudation into the pulmonary
interstitium and alveoli. Afterload reduction results in increased cardiac
output and improved renal perfusion, which allows for diuresis in the
patient with fluid overload. Inhibition of the RAAS and sympathetic
nervous system results in favored vasodilation and reduction of
neurohumoral vasoconstrictors, thereby increasing cardiac output and
reducing blood volume and myocardial oxygen demand.
Patients with severe LV dysfunction or acute valvular disorders may
present with hypotension. These patients may not tolerate medications to
reduce their preload and afterload and may require inotropic support to
maintain adequate blood pressure.
Patients who remain hypoxic despite supplemental oxygen or who
demonstrate severe respiratory distress require mechanical ventilation, in
addition to maximal medical therapy.
- Preload reduction
- Nitroglycerine (NTG) is the most effective, predictable, and
rapid-acting medication available for preload reduction.
- Multiple studies comparing NTG to furosemide or morphine sulfate
have demonstrated greater efficacy and safety and a faster onset of
action for NTG.
- Use of sublingual NTG is associated with preload reduction
within 5 minutes and some afterload reduction.
- Topical NTG may be as effective as sublingual NTG in most
patients with heart failure, but it should be avoided in patients
with severe LV failure because of poor skin perfusion (manifesting
as skin pallor or mottling) and resultant poor absorption.
- Intravenous NTG at higher dosages provides rapid and titratable
preload and afterload reduction and has been demonstrated to be an
excellent single-agent therapy for patients with severe
- Loop diuretics are the cornerstone of heart failure treatment
and have been considered as such for many decades. Furosemide is
most commonly used. Bumetanide has a higher bioavailability and may
be more effective in patients with severe CHF.
- Loop diuretics are presumed to decrease preload through 2
mechanisms: diuresis and direct pulmonary artery vasodilation and
- In most patients, diuresis does not occur for at least 20-90
minutes; thus, the effect is delayed.
- In some patients with heart failure, particularly those with
diastolic heart failure who are minimally fluid overloaded,
continued diuretic use after resolution of acute symptoms may be
associated with adverse outcomes, including electrolyte derangements
- Use of medications that decrease preload (eg, NTG) and afterload
(eg, ACE inhibitors), either concomitantly or before the
administration of loop diuretics, can prevent potential adverse
- Potassium-sparing diuretics
- Numerous studies have shown spironolactone to be as beneficial
in the management of CHF as loop diuretics.
- Some of the beneficial effects of spironolactone may be due to
its neurohormonal actions.
- Morphine sulfate use in acute CHF for preload reduction has been
commonplace for many years.
- Use should be weighed against potential adverse effects (eg,
nausea/vomiting, local or systemic allergic reactions, respiratory
depression) that may outweigh any potential benefit, especially
given the availability of much more effective medications for
preload reduction (eg, NTG).
- Any beneficial hemodynamic effect probably is due to anxiolysis,
with a resulting decrease in catecholamine production and systemic
- Vasodilators (combined afterload and preload reducers)
- Although initial studies focused on the efficacy of ACE
inhibitors in the treatment of chronic CHF, recent studies have
demonstrated excellent results for treatment of acute decompensated
- Studies demonstrate that the use of ACE inhibitors in acute
heart failure is associated with reduced admission rates to ICUs and
decreased endotracheal intubation rates.
- Hemodynamic effects of ACE inhibitors include reduced afterload,
improved stroke volume and cardiac output, and reduced preload.
- ACE inhibitors must be initiated with extreme care in
individuals presenting with borderline hemodynamic parameters.
- When administered by intravenous (enalapril 1.25 mg) or
sublingual routes, hemodynamic and subjective improvements are noted
within 10 minutes; improvements occur more slowly with the oral
- ACE inhibitors prolong survival in heart failure. Furthermore,
compared to the combination of hydralazine and long-acting nitrates,
ACE inhibitors showed a trend to a greater prolongation of survival,
had improved hemodynamics, and were better tolerated.
- Ang II receptor inhibitors
- Ang receptor inhibitors, such as losartan and candesartan, are
highly recommended alternatives to ACE inhibitors in patients who
cannot tolerate ACE inhibitors because of adverse effects, most
- Furthermore, these agents have gained wider use based on their
low adverse effect profile and early study findings, which indicated
that combined ACE inhibition and Ang II receptor inhibition is
- Hydralazine was the first oral balanced (afterload and preload
reduction) vasodilator and was popular before the availability of
ACE inhibitors. It is a direct vasodilator, unlike ACE inhibitors or
Ang receptor inhibitors, which are vasodilators through inhibition
of the RAAS system.
- When combined with long-acting nitrates, hydralazine was shown,
in the Veterans Administration Heart Failure Trial (VHEFT) studies,
to prolong survival in patients with CHF.
- Hydralazine has one main advantage over ACE inhibitors in that
it is safe in pregnancy. It also is not known to worsen renal
function in patients with heart failure who have reduced renal
function and is not associated with the risk of hyperkalemia.
Additionally, hydralazine use is recommended in patients who cannot
tolerate ACE inhibitors.
- Hydralazine, as a single agent, has less reduction in myocardial
oxygen demand than ACE inhibitors because of a slight increase in
heart rate that usually results from its use.
- Nitroprusside results in simultaneous preload and afterload
reduction through direct smooth muscle relaxation, although it has a
greater effect on afterload.
- Afterload reduction is associated with increased cardiac output.
- Potency and rapidity of onset and offset of effect make this an
ideal medication for patients who are critically ill.
- It may induce precipitous falls in blood pressure; intraarterial
blood pressure monitoring often is recommended.
- Use nitroprusside cautiously in the setting of acute myocardial
infarction because of its potential to induce hypotension.
- If nitroprusside is used, convert patients to oral or
alternative intravenous vasodilator therapy as soon as possible
because prolonged use is associated with thiocyanate toxicity.
- Use in pregnancy is associated with fetal thiocyanate
- Inotropic support
- Digoxin (cardiac glycoside)
- Digoxin has been a cornerstone for the treatment of heart
failure for decades and is the only oral inotropic support agent
currently used in clinical practice.
- Digoxin acts by inhibiting the
Na+/K+–ATPase transport pump and inhibits
sodium and potassium transport across cell membranes. This increases
the velocity and shortening of cardiac muscle, resulting in a shift
upward and to the left of the ventricular function (Frank-Starling)
curve relating stroke volume to filling volume or pressure. This
occurs in healthy as well as failing myocardium and in atrial as
well as ventricular muscle. The positive inotropic effect is due to
an increase in the availability of cytosolic calcium during systole,
thus increasing the velocity and extent of myocardial sarcomere
- No evidence indicates that digoxin affects peripheral vascular
resistance or systemic blood pressure.
- All evidence suggests that digoxin provides, even in the short
term, a moderate and metabolically efficient positive inotropic
effect, an important consideration in ischemic cardiomyopathies.
- Although the incidence and severity of digitalis intoxication is
decreasing, vigilance for this important complication of therapy is
essential. Drugs that interact with digoxin are numerous and include
amiodarone, propafenone, quinidine, verapamil, nifedipine,
diltiazem, levothyroxine, cyclosporine, flecainide, disopyramide,
omeprazole, tetracycline, and erythromycin. These agents affect
clearance or absorption of digoxin, thus necessitating dose
alteration of digoxin in patients taking these medications.
Furthermore, patients with renal insufficiency may need to have
their digoxin dose adjusted downward to avoid digitalis
- Numerous studies confirm that digoxin does not prolong survival
in patients with systolic heart failure, but it is associated with
reduced hospital admissions, improved functional class, reduced
symptoms of heart failure, and improved quality of life.
- Digoxin is also an effective agent against atrial
tachyarrhythmias at rest in patients with LV dysfunction, but it has
limited efficacy in controlling the ventricular rate of atrial
arrhythmias during exertion.
- Dobutamine (sympathomimetic agent)
- Dobutamine mainly serves as a beta1-receptor agonist, although
it has some beta2-receptor and minimal alpha-receptor activity.
- Intravenous dobutamine induces significant positive inotropic
effects with mild chronotropic effects. It also induces mild
peripheral vasodilation (decrease in afterload).
- The combination effect of increased inotropy with decreased
afterload results in a significant increase in cardiac output.
- Combination use with intravenous NTG may be ideal for patients
with myocardial infarction and decompensated heart failure and mild
hypotension in order to provide simultaneous preload reduction with
increased cardiac output. In the setting of acute myocardial
infarction, dobutamine use could increase infarct size because of
the increase in myocardial oxygen consumption that may ensue.
- In general, avoid dobutamine in patients with moderate or severe
hypotension (eg, systolic blood pressure <80 mm Hg) because of
the peripheral vasodilation.
- Dopamine (sympathomimetic agent)
- Vascular and myocardial receptor effects are dose dependent.
- Low dosages (0.5-3 mcg/kg/min) cause stimulation of dopaminergic
receptors within the renal and splanchnic vascular beds, causing
vasodilation and increased diuresis.
- Moderate dosages (3-10 mcg/kg/min) cause stimulation of
beta-receptors in the myocardium, resulting in increased cardiac
contractility and heart rate.
- High dosages (10-20 mcg/kg/min) cause stimulation of
alpha-receptors, resulting in peripheral vasoconstriction (increased
afterload), increased blood pressure, and no further improvement in
- As with other inotropic agents, moderate and high dosages are
arrhythmogenic and also result in increased myocardial oxygen demand
(potential for myocardial ischemia); therefore, use dopamine only in
patients with heart failure who cannot tolerate the use of
dobutamine because of severe hypotension (eg, systolic blood
pressure <60-80 mm Hg).
- NE (sympathomimetic agent)
- NE primarily stimulates alpha-receptors, resulting in
significant increases in afterload (and potential myocardial
ischemia) and reduced cardiac output.
- Use of NE is generally reserved for patients with profound
hypotension (eg, systolic blood pressure <60 mm Hg). Once blood
pressure is restored, add other medications to maintain cardiac
- Phosphodiesterase inhibitors (milrinone, amrinone)
- Phosphodiesterase inhibitors (PDIs) increase intracellular cAMP,
which results in a positive inotropic effect on the myocardium and
peripheral vasodilation (decreased afterload) and a reduction in
pulmonary vascular resistance (decreased preload).
- PDIs, unlike catecholamine inotropes, are not dependent on
adrenoreceptor activity; therefore, patients are less likely to
develop tolerance to these medications. Tolerance to catecholamine
inotropes can develop rapidly through down-regulation of the
- PDIs are less likely than catecholamine inotropes to cause
adverse effects that are typically associated with adrenoreceptor
activity (eg, increased myocardial oxygen demand, myocardial
- Several studies directly comparing the use of PDIs (milrinone,
amrinone) to dobutamine in patients with heart failure have
demonstrated that milrinone produced equal or greater improvements
in stroke volume, cardiac output, PCWPs (preload), and systemic
vascular resistance (afterload). They are also associated with less
tachycardia and myocardial oxygen consumption. However, PDIs have
been associated with a significantly greater incidence of adverse
events (eg, tachyarrhythmias) than has dobutamine.
- At present, oral PDIs have no role. Their use was associated
with a 53% increase in mortality rates in patients with NYHA Class
IV heart failure in the Prospective Randomized Milrinone Survival
Evaluation (PROMISE) trial, prompting an early termination of that
- Unfavorable results were also evident in a smaller trial that
compared oral milrinone to digoxin or placebo. Furthermore,
sustained hemodynamic improvement with oral milrinone was lacking,
and the incidence of adverse events, particularly cardiac
arrhythmias, was greater.
- Beta-adrenergic blocking agents (metoprolol, carvedilol)
- A large and increasing body of evidence indicates that these
agents improve symptoms, exercise tolerance, cardiac hemodynamics, and
LV ejection fraction and that they decrease mortality rates in
patients with heart failure, particularly those with both ischemic and
- A growing body of evidence suggests that long-term beta-adrenergic
antagonist administration improves cardiac function, reduces
myocardial ischemia, improves ventricular-arterial coupling, and
decreases myocardial oxygen consumption. These agents may also reduce
the incidence of sudden death due to primary ventricular arrhythmias
in patients with heart failure, although this latter benefit has yet
to be definitively proven.
- Detectable improvements in ventricular function are usually not
apparent for a minimum of 1-3 months, and longer-term structural
changes, such as a decline in ventricular volume or mass, may take
- Beta-adrenergic antagonists with vasodilator activity, such as
carvedilol and labetalol, have the added benefit of further afterload
reduction because of arterial vasodilation from alpha1-receptor
- Treatment of heart failure with predominant diastolic dysfunction:
The therapeutic approach to diastolic dysfunction has 2 major
components. The first involves attempts to reverse the abnormal cardiac
diastolic properties. The second is directed toward reducing LV filling
pressure and thereby venous congestion.
- Treatment of diastolic dysfunction
- Pericardiectomy for constrictive pericarditis
- Relief of ventricular systolic overload
- ACE inhibitors and Ang receptor inhibitors slow, arrest, or
even reverse myocardial fibrosis in the presence of systolic
overload, thus improving diastolic dysfunction.
- Anti-ischemic agents, such as beta-adrenergic blocking agents,
calcium channel blocking agents, and nitroglycerin, are effective
in immediately improving diastolic dysfunction in patients with
coronary artery disease by eliminating or reducing myocardial
ischemia, thus improving ventricular relaxation. Thrombolysis,
mechanical revascularization (percutaneous transluminal coronary
angioplasty [PTCA]), and coronary artery bypass graft surgery
(CABGS), in combination with anti-ischemic agents or alone, all
improve diastolic function in patients with acute and chronic
myocardial ischemia by improving ventricular relaxation.
- Calcium channel antagonists, especially verapamil, accelerate
ventricular relaxation, particularly in patients with hypertensive
heart disease and hypertrophic cardiomyopathy, and are useful in
the treatment of diastolic dysfunction.
- Regression of ventricular hypertrophy
- Aggressive control of hypertension with beta-adrenergic
blocking agents, calcium channel blocking agents, diuretics, ACE
inhibitors, Ang receptor inhibitors, and central-acting
antihypertensive agents (eg, methyldopa) reduces ventricular
hypertrophy, thereby improving diastolic function.
- Aortic valve replacement for aortic stenosis also reduces
ventricular hypertrophy and improves diastolic function.
- Relief of valvular, supravalvular, and subvalvular obstruction
to ventricular outflow by operation or balloon valvuloplasty
improves diastolic function by relieving ventricular pressure
overload, thus regressing ventricular hypertrophy.
- Reduction of ventricular filling pressure and secondary venous
congestion: These approaches are usually highly effective in patients
presenting with a CHF exacerbation primarily caused by a diastolic
dysfunction. Indeed, a hallmark of diastolic dysfunction is the rapid
improvement in response to the therapies described below.
- Restriction of dietary sodium
- Administration of diuretics and venodilators
- Administration of NTG or long-acting nitrates
- Maintenance of normal heart rate and rhythm: Digoxin has no
established place in the management of patients with predominant
diastolic dysfunction and well-preserved ventricular ejection
fraction, and it could potentially have an adverse effect in this
group of patients.
- Newer therapies for heart failure
- Nesiritide, a recombinant BNP, is from an exciting new class of
peptides that has several unique properties.
- Nesiritide is a balanced vasodilator, slightly more venous than
arterial, rapidly improves symptoms of congestion, does not increase
heart rate, decreases myocardial oxygen demand, and is not
- Nesiritide decreases aldosterone and ET-1 release through
neurohumoral suppression, does not exhibit tachyphylaxis, and
induces a mild diuresis and natriuresis. It significantly reduces
ventricular filling pressures to a greater extent than standard care
with ACE inhibitors and diuretics, even more than the combination of
ACE inhibitors, diuretics, and nitroglycerin.
- Nesiritide should be avoided in patients with systolic blood
pressure of less than 80-85 mm Hg. The primary adverse event
(occurring in 4% of the patients in the Veterans Administration
Medical Center [VAMC] study on nesiritide) was hypotension.
- Nesiritide has no drug interactions with any of the other
treatments used in CHF, thus making it useful as an effective
adjunct in patients with severe, acute decompensated CHF without
- Study results indicate that treatment with nesiritide could lead
to a reduced length of stay in the critical care unit, decreased
recurrence of decompensation, and less likelihood of
- Eplerenone, a selective aldosterone-blocking agent, has been shown
to reduce rates of all-cause mortality, cardiovascular mortality, and
sudden cardiac death in patients with myocardial infarction and left
ventricular systolic dysfunction who are in CHF and already being
treated with a beta-blocker and an ACE inhibitor or Ang II blocker.
Close monitoring of potassium levels and appropriate dosage
adjustments or use of diuretics are necessary because a small
percentage of patients taking eplerenone develop
Surgical Care: Kantrowitz initially described
intraaortic balloon pumping (IABP) in 1953, but the procedure was first
used clinically in 1969 in a patient with cardiogenic shock. Since the
1980s, IABP has been increasingly used in various clinical situations as a
lifesaving intervention to obtain hemodynamic stabilization prior to
- The intraaortic balloon pump is inserted percutaneously via the
femoral artery using a modified Seldinger technique. The distal end of
the pump is placed just distal to the aortic knob and the origin of
left subclavian artery.
- Fluoroscopy may be used for correct positioning of the balloon,
and a subsequent chest radiograph should be obtained to document
satisfactory balloon placement.
- Proper timing of IABP for optimal hemodynamic support
- Proper timing of counterpulsation is necessary for maximum
hemodynamic support. The timings of balloon inflation and deflation
are best evaluated and adjusted at a pump frequency of 1:2.
- Inflation of the balloon should occur in early diastole, just
after aortic valve closure, and should correspond to the dicrotic
notch of the aortic pressure waveform. Balloon deflation should occur
in early systole, just before the aortic valve opens.
- Proper inflation leads to an assisted peak diastolic pressure
higher than the unassisted peak systolic arterial pressure. Proper
deflation results in assisted aortic end-diastolic pressure
approximately 10 mm Hg lower than the unassisted end-diastolic
- Diastolic augmentation enhances perfusion of the coronary
circulation and carotid arteries. The reduction in end-diastolic
pressure decreases aortic impedance (afterload) and augments systole.
- IABP reduces aortic impedance and systolic pressure, leading to a
15-25% reduction in LV wall stress. This level of afterload reduction
improves LV volume, LV emptying, and myocardial oxygen consumption.
- Diastolic aortic pressure augmentation enhances myocardial
perfusion and coronary blood flow. The effects on coronary blood flow
may be variable but generally range from a boost of 10-20% in ischemic
- IABP can decrease LV filling pressures by 20-25% and can improve
cardiac output by 20% in patients with cardiogenic shock; therefore,
IABP reduces myocardial oxygen demand significantly, although the
beneficial effect of increased oxygen supply to the myocardium may
also occur in some clinical situations.
- IABP is very effective in providing temporary support to patients
in cardiogenic shock while definite therapies such as angioplasty or
cardiac bypass surgery are undertaken. At most institutions, IABP is
generally considered to be a bridge to a definite revascularization
procedure or to implementation of an LV assist device.
- IABP is effective in stabilizing patients with unstable angina
refractory to medical therapy prior to a definitive revascularization
- IABP may be a lifesaving intervention in patients with acute
mitral regurgitation secondary to papillary muscle ischemia,
infarction, and other causes such as infectious endocarditis or
myxomatous degeneration. IABP reduces afterload (thereby reducing the
severity of mitral regurgitation), enhances forward cardiac output,
reduces left atrial pressure, and improves pulmonary edema.
- IAPB is used to stabilize patients, which allows time to plan the
definitive surgical procedure in patients who are hemodynamically
- IABP could also provide hemodynamic support in the perioperative
and postoperative period.
- Contraindications and complications
- The absolute contraindications for IABP counterpulsation are
aortic dissection, severe aortic regurgitation, presence of a large
arteriovenous shunt, and severe coagulopathy.
- The relative contraindications are severe peripheral vascular
disease, recent thrombolytic therapy, and bleeding diathesis.
- IABP can cause several complications that should be monitored
while the patient is maintained on IABP support. Generally, a mild
reduction in platelet counts occurs; however, these usually do not
fall below 100,000/mL
- Complications may occur during cannulation of the femoral artery
and include perforation, laceration, or dissection of the artery
(1-6%). Thrombosis of the iliofemoral artery and distal emboli may
also occur (1-7%), and limb ischemia has been reported in up to 40% of
patients. The limb ischemia is reversible upon removing the
intraaortic balloon pump unless thrombosis has developed, which
requires embolectomy to save the limb.
- The other complications are localized bleeding (3-5%), infection
(2-4%), thrombocytopenia (<1%), and intestinal ischemia
- Ventricular assist device: This is generally considered a short-term
therapy (eg, acute myocarditis) or bridge to transplant, though a recent
study suggested improved survival when used long term.
- Biventricular pacing (cardiac resynchronization): A new therapy,
biventricular pacing may improve left ventricular pumping efficacy in
patients with relatively severe cardiomyopathy and wide QRS
Consultations: Consultation with subspecialists
depends on the underlying cause of CHF. Heart failure is now an area of
subspecialization within cardiology.
- If the acute episode is attributed to an acute myocardial
infarction, acute cardiac ischemia, or acute dysrhythmia, consultation
with a cardiologist is warranted.
- If the episode is attributed to fluid overload in patients with
renal failure, consultation with a nephrologist is indicated for
- If heart failure results from acute valvular dysfunction,
consultation with a cardiothoracic surgeon and a cardiologist for urgent
valve replacement may be indicated, depending on the integrity of the
- In patients who develop cardiogenic shock, consultation with a
cardiologist is generally indicated in order to rapidly diagnose and
aggressively treat with various modalities (pharmacologic and/or
mechanical), to maximize cardiac performance and improve hemodynamics,
and, in some cases, to place an intraaortic balloon pump to serve as a
temporizing measure prior to surgery (ie, for valve replacement or
Diet: Patients admitted with heart failure or
pulmonary edema should maintain a low-salt diet in order to minimize fluid
overload. Monitor fluid balance closely.
- Patients with decompensated heart failure should be placed on
complete bed rest until their decompensation is resolved. This is
necessary to maximally reduce myocardial oxygen demand and to avoid
exacerbation of the abnormal hemodynamics and symptoms of heart
- Once the patient with heart failure has been stabilized, activity
should be gradually and progressively increased. Emphasize the
importance of cardiac rehabilitation to all patients with heart failure
who require improved cardiac fitness. Encourage patients to exercise
daily for at least 20-30 minutes in a low-intensity, endurance-enhancing
activity such as walking, biking, or swimming. Regular exercise improves
the quality of life for these patients and improves efficiency of oxygen
utilization at the tissue level, thus reducing the workload of the heart
in the role of oxygen delivery to end organs and muscles.
||Section 7 of 10 |
The goals of pharmacotherapy are to
reduce morbidity and to prevent complications.
Drug Category: Human B-type natriuretic peptides
(hBNPs) -- Dilate veins and arteries. Used in the treatment of
acute severe CHF.
Drug Category: Diuretics -- May improve symptoms of
venous congestion through elimination of retained fluid and preload
reduction. Used in CHF. Help counteract the sodium and water retention
caused by activation of the RAAS.
||Nesiritide (Natrecor) --
Recombinant DNA form of hBNP, which dilates veins and arteries. hBNP
binds to particulate guanylate cyclase receptor of vascular smooth
muscle and endothelial cells. Binding to receptor causes increase in
cGMP, which serves as second messenger to dilate veins and arteries.
Reduces PCWP and improves dyspnea in patients with acutely
||2 mcg/kg IV bolus over 60 sec;
follow by 0.01 mcg/kg/min continuous infusion; bolus volume (mL) =
0.33 X patient weight (kg); infusion flow rate of bolus (mL/h) = 0.1
X patient weight (kg)
systolic blood pressure <90 mm Hg; patients suspected of having
or known to have low cardiac filling pressures, severe aortic or
mitral stenosis, restrictive or obstructive cardiomyopathy,
constrictive pericarditis, pericardial tamponade, conditions in
which cardiac output is dependent upon venous return
||Concurrent administration with ACE
inhibitors and other vasodilators may cause hypotension
||C - Safety for use during pregnancy
has not been established.
||Do not initiate at dose higher than
recommended; may affect renal function in patients whose renal
function may depend on activity of RAAS; may cause hypotension
(administer in settings where blood pressure can be monitored
closely); discontinue drug if hypotension develops; VT, nonsustained
VT, headache, abdominal pain, back pain, insomnia, anxiety, angina
pectoris, nausea, and vomiting may occur|
||Furosemide (Lasix); Bumetanide
(Bumex); Torsemide (Demadex) -- Increase excretion of water by
interfering with chloride-binding cotransport system, which in turn
inhibits sodium and chloride reabsorption in ascending loop of Henle
and distal renal tubule. Bumetanide does not appear to act in the
distal renal tubule. Dose must be individualized to patient.
Depending on response, administer at small dose increments until
desired diuresis occurs.
||Furosemide: 20-80 mg/d PO/IV/IM;
titrate up to 600 mg/d for severe edematous states; depending on
response, administer at increments of 20-40 mg no sooner than 6-8 h
after previous dose
Bumetanide: 0.5-2 mg/dose PO 1-2 times/d; titrate dose upward
until desired diuretic effect reached; not to exceed 10 mg/d;
alternatively, 0.5-1 mg/dose IV/IM; not to exceed 10 mg/d
Torsemide: 10-20 mg PO/IV qd; not to exceed 200 mg/d; titrate
dose upward by approximately doubling the dose until desired
diuretic effect reached; doses >200 mg/d not adequately
||Furosemide: 1-2 mg/kg/dose PO; not
to exceed 6 mg/kg/dose; not to administer more frequently than
Bumetanide: Not established
hepatic coma, anuria, increasing anuria, and state of severe
||Potential for salicylate toxicity
in patients on high doses of salicylates and loop diuretics
significant (salicylates and loop diuretics compete for secretion by
renal tubules); NSAIDs may decrease efficacy of loop diuretics; loop
diuretics increase potential for lithium toxicity; simultaneous use
of loop diuretics and cholestyramine not recommended as
cholestyramine decreases absorption of loop diuretics; probenecid
decreases effect loop diuretics; coadministration with
aminoglycosides may increase ototoxicity; enzyme inducers, including
phenytoin, carbamazepine, and phenobarbital, may reduce efficacy of
loop diuretics; hypotensive effects of ACE inhibitors may increase
when administered concomitantly with loop diuretics; arrhythmias may
occur in patients taking digoxin if diuretic-induced electrolyte
||C - Safety for use during pregnancy
has not been established.
||Torsemide is pregnancy category B;
perform frequent serum electrolyte, CO2, glucose,
creatinine, uric acid, calcium, and BUN determinations during first
few months of therapy and periodically thereafter; profound diuresis
with fluid and electrolyte loss may occur; caution in hepatic
Drug Category: Angiotensin
receptor blockers -- Interfere with the binding of formed Ang
II to its endogenous receptor. Used primarily when patients are intolerant
of ACE inhibitors because of adverse effects but are gaining wider use as
first-line vasodilator agents. Equally effective as ACE inhibitors.
||Spironolactone (Aldactone) -- For
management of edema resulting from excessive aldosterone excretion.
Competes with aldosterone for receptor sites in distal renal
tubules, increasing water excretion while retaining potassium and
||25-200 mg/d PO qd or divided bid
||1.5-3.5 mg/kg/d PO qd or divided
anuria, renal failure, hyperkalemia
||May decrease effect of
anticoagulants; potassium and potassium-sparing diuretics may
increase toxicity of spironolactone
||D - Unsafe in pregnancy
||Caution in renal and hepatic
Drug Category: ACE
inhibitors -- Inhibit renal systemic and tissue generation of
Ang II by ACE; decrease metabolism of bradykinin (BK). Their blockade of
Ang II and the delayed clearance of BK by ACE blocks the direct
vasoconstriction of Ang II, as well as the activation of the sympathetic
nervous system, and promotes arterial and venous dilation. In addition,
ACE inhibitors reduce intracavitary pressures and diminish Wass stress,
thereby decreasing myocardial oxygen demand. They inhibit the release of
aldosterone, thereby reducing intravascular volume and preload. Among
vasodilators, the ACE inhibitors are the most balanced vasodilators,
having an equal effect on reducing both afterload and preload.
||Losartan (Cozaar); Candesartan
(Atacand); Valsartan (Diovan) -- Block the vasoconstrictor and
aldosterone-secreting effects of Ang II. May induce more complete
inhibition of RAAS than ACE inhibitors, do not affect response to
BK, and are less likely to be associated with cough and angioedema.
For patients unable to tolerate ACE inhibitors.
||Losartan: 25-100 mg PO
Candesartan: 8-16 mg/d PO initially; not to exceed 32
Valsartan: 80 mg/d PO; may increase to 160 mg/d if
||Ketoconazole, sulfaphenazole, and
phenobarbital may decrease effects; cimetidine may increase effects
of losartan and candesartan
||C - Safety for use during pregnancy
has not been established.
||Category D in second and third
trimesters of pregnancy; caution in renal impairment (serum
creatinine >3.5), severe aortic stenosis, unilateral or bilateral
renal artery stenosis or severe CHF; watch for serum
Vasodilators -- The use of a vasodilators reduces SVR,
thus allowing more forward flow and improving cardiac output. Indicated
||Captopril (Capoten); Enalapril
(Vasotec); Quinapril (Accupril) -- Lisinopril (Prinivil, Zestril);
Ramipril (Altace); Fosinopril (Monopril)--Prevent conversion of Ang
I to Ang II (a potent vasoconstrictor), resulting in increased
levels of plasma renin and a reduction in aldosterone secretion.
||Captopril: 6.25-12.5 mg PO tid; not
to exceed 150 mg tid|
Enalapril: 2.5-5 mg/d PO (increase as
necessary); dosing range: 10-40 mg/d PO in 1-2 divided doses;
alternatively, 1.25 mg/dose IV over 5 min q6h
mg PO qd
Lisinopril: 10 mg/d PO qd or divided bid; increase
by 5-10 mg/d at 1- to 2-wk intervals; not to exceed 80
Ramipril: 2.5 mg PO bid initially; titrate up to 5 mg
bid when possible
Fosinopril: 10 mg/d PO initially; may
increase to 20-40 mg/d qd or divided bid
||Documented hypersensitivity; renal
||NSAIDs may reduce hypotensive
effects of ACE inhibitors; ACE inhibitors may increase digoxin,
lithium, and allopurinol levels; rifampin decreases ACE inhibitor
levels; probenecid may increase ACE inhibitor levels; hypotensive
effects of ACE inhibitors may be enhanced when concurrently
administered with diuretics
||D - Unsafe in pregnancy
||Category D in second and third
trimester of pregnancy; caution in renal impairment, valvular
stenosis, or severe CHF|
||Nitroglycerin (Nitrostat, Deponit,
Transderm-Nitro Patch) -- Isosorbide dinitrate (Isordil), Isosorbide
mononitrate (Imdur)--First-line therapy for patients who are not
hypotensive. Provides excellent and reliable preload reduction.
Higher doses provide mild afterload reduction. Has rapid onset and
offset (both within minutes), allowing rapid clinical effects and
rapid discontinuation of effects in adverse clinical situations.
topically 1/2-2" q6h
Transdermal: 0.3-0.6 mg/h
Intravenous: 0.2-10 mcg/kg/min IV infusion; titrate by 10
mcg/min increments until desired hemodynamic effect achieved or
until maximally tolerated dose reached
Spray: Single spray
(0.4 mg), which is equivalent to single 1/150 sublingual; dose may
be repeated q3-5min as hemodynamics permit, up to maximum of 1.2
Isosorbide dinitrate: 10-80 mg PO
Isosorbide mononitrate: 30-90 PO mg qd
hypotension; severe anemia; shock; postural hypotension; head
trauma; closed-angle glaucoma; cerebral hemorrhage
||Sildenafil (Viagra) taken within 24
h may induce precipitous and potentially lethal decreases in blood
pressure; aspirin may increase nitrate serum concentrations; marked
symptomatic orthostatic hypotension may occur with coadministration
of calcium channel blockers (dose adjustment of either agent may be
||C - Safety for use during pregnancy
has not been established.
||Extreme caution in right ventricle
infarction because of importance of adequate preload in maintaining
cardiac output; caution in patients with severe aortic stenosis
because of needed adequate preload to maintain cardiac
||Hydralazine (Apresoline) --
Decreases systemic resistance through direct vasodilation of
||10-25 mg PO tid/qid initially;
adjust dose based on individual response; typical dose range is
200-600 mg PO qd in 2-4 divided doses
||Documented hypersensitivity; mitral
valve rheumatic heart disease
||MAOIs and beta-blockers may
increase hydralazine toxicity; pharmacologic effects of hydralazine
may be decreased by indomethacin
||B - Usually safe but benefits must
outweigh the risks.
||Hydralazine has been implicated in
myocardial infarction; caution in suspected coronary artery
Drug Category: Inotropic
agents -- Augment both coronary and cerebral blood flow
present during the low flow states. Used in severe acute CHF with low
||Nitroprusside (Nitropress) --
Produces vasodilation and increases inotropic activity of the heart.
At higher dosages, may exacerbate myocardial ischemia by increasing
||Begin infusion at 0.3-0.5
mcg/kg/min IV and use increments of 0.5 mcg/kg/min; titrate to
desired effect; average dose is 1-6 mcg/kg/min|
>10 mcg/kg/min may lead to cyanide toxicity
||Administer as in adults
subaortic stenosis, decreased cerebral perfusion, arteriovenous
shunt or coarctation of aorta (eg, compensatory hypertension);
relatively contraindicated in atrial fibrillation or flutter with
rapid ventricular rate
||Effects are additive when
administered with other hypotensive agents
||C - Safety for use during pregnancy
has not been established.
||Caution in increased intracranial
pressure, hepatic failure, severe renal impairment, and
hypothyroidism; in renal or hepatic insufficiency, nitroprusside
levels may increase and can cause cyanide toxicity; sodium
nitroprusside has ability to lower blood pressure and thus should be
used only in those patients with mean arterial pressures >70 mm
||Digoxin (Lanoxin, Lanoxicaps) --
Cardiac glycoside with direct inotropic effects in addition to
indirect effects on cardiovascular system. Acts directly on cardiac
muscle, increasing myocardial systolic contractions. Indirect
actions result in increased carotid sinus nerve activity and
enhanced sympathetic withdrawal for any given increase in mean
||0.125-0.375 mg PO qd
beriberi heart disease, idiopathic hypertrophic subaortic stenosis,
constrictive pericarditis, and carotid sinus syndrome
||IV calcium may produce arrhythmias
in digitalized patients; medications that may increase digoxin
levels include alprazolam, benzodiazepines, bepridil, captopril,
cyclosporine, propafenone, propantheline, quinidine, diltiazem,
aminoglycosides, oral amiodarone, anticholinergics, diphenoxylate,
erythromycin, felodipine, flecainide, hydroxychloroquine,
itraconazole, nifedipine, omeprazole, quinine, ibuprofen,
indomethacin, esmolol, tetracycline, tolbutamide, and verapamil;
medications that may decrease serum digoxin levels include
aminoglutethimide, antihistamines, cholestyramine, neomycin,
penicillamine, aminoglycosides, oral colestipol, hydantoins,
hypoglycemic agents, antineoplastic treatment combinations
(including carmustine, bleomycin, methotrexate, cytarabine,
doxorubicin, cyclophosphamide, vincristine, procarbazine), aluminum
or magnesium antacids, rifampin, sucralfate, sulfasalazine,
barbiturates, kaolin/pectin, and aminosalicylic acid
||C - Safety for use during pregnancy
has not been established.
||Hypokalemia may reduce positive
inotropic effect of digitalis; hypercalcemia predisposes patient to
digitalis toxicity, and hypocalcemia can make digoxin ineffective
until serum calcium levels are normal; magnesium replacement therapy
must be instituted in patients with hypomagnesemia to prevent
digitalis toxicity; patients diagnosed with incomplete AV block may
progress to complete block when treated with digoxin; exercise
caution in hypothyroidism, hypoxia, and acute myocarditis; adjust
dose in renal impairment; highly toxic (overdoses can be
||Dobutamine (Dobutrex) -- Produces
vasodilation and increases inotropic state. At higher dosages may
cause increased heart rate, exacerbating myocardial ischemia.
||0.5 mcg/kg/min IV initially;
titrate until desired therapeutic effect attained
||Administer as in adults
idiopathic hypertrophic subaortic stenosis and atrial fibrillation
||Beta-adrenergic blockers antagonize
effects of dobutamine; general anesthetics may increase toxicity
||B - Usually safe but benefits must
outweigh the risks.
||Following a myocardial infarction
use with extreme caution; hypovolemic state should be corrected
before using this drug|
||Dopamine (Intropin) -- Naturally
occurring catecholamine that acts as a precursor to NE. Stimulates
both adrenergic and dopaminergic receptors. Hemodynamic effect is
dose-dependent. Low-dose use is associated with dilation within
renal and splanchnic vasculature, resulting in enhanced diuresis.
Moderate doses enhance cardiac contractility and heart rate. Higher
doses cause increased afterload through peripheral
Administer by continuous IV infusion.
Usually used in severe heart failure. Reserved for patients with
moderate hypotension (eg, systolic blood pressure 70-90 mm Hg).
Typically, moderate or higher doses used.
||5 mcg/kg/min IV continuous infusion
initially; titrate to blood pressure stabilization; not to exceed 20
pheochromocytoma; ventricular fibrillation; obstructive hypertrophic
||Phenytoin, alpha- and
beta-adrenergic blockers, general anesthesia, and MAOIs increase and
prolong effects of dopamine
||C - Safety for use during pregnancy
has not been established.
||Monitor urine flow, cardiac output,
pulmonary wedge pressure, and blood pressure closely during
infusion; prior to infusion, correct hypovolemia with either whole
blood or plasma as indicated; monitoring central venous pressure or
LV filling pressure may be helpful in detecting and treating
hypovolemia; 10- to 20-mcg/kg/min doses increase levels of
peripheral vasoconstriction and afterload; may increase
tachyarrhythmias and cause greater myocardial oxygen consumption and
cardiac ischemia; alkaline solutions may inactivate dopamine if
administered through same IV line|
Drug Category: Phosphodiesterase enzyme inhibitors
-- Inhibition of type III cAMP phosphodiesterase(s) and other
mechanisms. Bipyridine-positive inotropic agents and vasodilators with
little chronotropic activity. Different from both digitalis glycosides and
catecholamines in mode of action. These agents are balanced vasodilators,
having equal reduction in both afterload and preload, to same degree as
||Norepinephrine (Levophed) --
Naturally occurring catecholamine with potent alpha-receptor and
mild beta-receptor activity. Stimulates beta1- and alpha-adrenergic
receptors, resulting in increased cardiac muscle contractility,
heart rate, and vasoconstriction. Increases blood pressure and
afterload. Increased afterload may result in decreased cardiac
output, increased myocardial oxygen demand, and cardiac ischemia.
Generally reserved for use in patients with severe hypotension (eg,
systolic blood pressure <70 mm Hg) or hypotension unresponsive to
||0.5-1 mcg/min IV infusion
initially, titrated to effect; not to exceed 30 mcg/min
obstructive hypertrophic cardiomyopathy; peripheral or mesenteric
vascular thrombosis because ischemia may be increased and area of
||Enhances pressor response of NE by
blocking reflex bradycardia caused by NE
||C - Safety for use during pregnancy
has not been established.
||May cause tachyarrhythmia
(especially sinus tachycardia), increased myocardial oxygen demand,
and cardiac ischemia; alkaline solutions may inactivate NE if
administered through same IV line; extravasation may cause severe
tissue necrosis, (administer into a large vein); if extravasation
occurs, immediately infiltrate 5-10 mg of phentolamine (diluted in
10-15 mL of isotonic sodium chloride solution) to prevent necrosis;
caution in occlusive vascular disease; if possible, correct
blood-volume depletion before administration|
Beta-adrenergic blockers -- Inhibit chronotropic,
inotropic, and vasodilatory responses to beta-adrenergic stimulation.
Particularly useful in the patient with elevated blood pressure and
relative tachycardia. Inhibits sympathetic nervous stimulation,
particularly E and NE and blocks alpha1-adrenergic vasoconstrictor
activity. Has moderate afterload reduction properties and results in
slight preload reduction as well.
||Milrinone (Primacor), Amrinone
(Inocor) -- Milrinone: Positive inotropic agent and vasodilator.
Results in reduced afterload, reduced preload, and increased cardiac
output. Several studies comparing milrinone to dobutamine have
demonstrated that milrinone showed greater improvements in preload
and afterload and improvements in cardiac output, without
significant increases in myocardial oxygen consumption.
Amrinone: Produces vasodilation and increases inotropic state.
More likely to cause tachycardia than dobutamine; may exacerbate
||Milrinone: 50 mcg/kg IV loading
dose over 10 min, followed by continuous infusion at 0.25-1.0
mcg/kg/min; titrate to maintain adequate systolic blood pressure and
Amrinone: 0.75 mg/kg IV bolus slowly over 2-3 min; maintenance
infusion is 5.0-10 mcg/kg/min; not to exceed 10 mg/kg; adjust dose
according to patient response; not to exceed 10 mg/kg
||Milrinone: Not established
Amrinone: Administer as in adults
hypersensitivity; obstructive hypertrophic cardiomyopathy
Amrinone: Documented hypersensitivity
||Milrinone: Precipitates in presence
Amrinone: Coadministration with diuretics may result in
hypovolemia and decrease in filling pressure; cardiac glycosides
have additive effects on amrinone
||C - Safety for use during pregnancy
has not been established.
||Milrinone: Monitor fluids,
electrolyte changes, and renal function during therapy; excessive
diuresis may increase potassium loss and predispose digitalized
patients to arrhythmias (correct hypokalemia with potassium
supplementation prior to treatment); slow rates or stop infusion in
patients showing excessive decreases in blood pressure; previous
vigorous diuretic therapy has caused significant decreases in
cardiac filling pressure; administer cautiously and monitor blood
pressure, heart rate, and clinical symptomatology
Amrinone: Discontinue therapy if symptoms of liver toxicity
develop; correct hypokalemic states before administering
||Carvedilol (Coreg) -- Nonselective
beta- and alpha1-adrenergic blocker. Does not appear to have
intrinsic sympathomimetic activity. May reduce cardiac output and
decrease peripheral vascular resistance.
||3.125 mg PO bid; maintain for 1-2
wk if tolerated and double dose q1-4wk to maximally tolerated dose
or to maximum of 50 mg bid
hypotension; bradycardia; AV/SA node disease; cardiogenic shock;
overt cardiac failure
cholestyramine, colestipol, NSAIDs, salicylates, and penicillins may
decrease effects; carvedilol may increase effects of antidiabetic
agents, digoxin, and calcium channel blockers; concurrent
administration with clonidine may increase blood pressure and
decrease heart rate; carvedilol may decrease effect of
sulfonylureas; cimetidine, fluoxetine, paroxetine, and propafenone
may increase carvedilol levels
||C - Safety for use during pregnancy
has not been established.
||Caution in CHF being treated with
digitalis, diuretics, or ACE inhibitors (AV conduction may be
slowed); discontinue if liver impairment occurs; caution in
peripheral vascular disease, hyperthyroidism, and diabetes
||Metoprolol XL (Toprol) -- Selective
beta1-adrenergic blocker at lower doses; inhibits beta2-receptors at
higher doses. Does not have intrinsic sympathomimetic activity. May
reduce cardiac output, but does not appear to decrease peripheral
vascular resistance to any significant degree.
||100 mg PO qd; titrate to maximum
dose of 400 mg/d PO in 1-2 divided doses.
hypotension; bradycardia; AV/SA node disease; cardiogenic shock;
overt cardiac failure
cholestyramine, colestipol, NSAIDs, salicylates, and penicillins may
decrease effects; high doses of metoprolol XL may increase effects
of antidiabetic agents, digoxin, and calcium-channel blockers
because of beta2-receptor inhibition; concurrent administration with
clonidine may increase blood pressure and decrease heart rate;
metoprolol XL may decrease effect of sulfonylureas; cimetidine,
fluoxetine, paroxetine, and propafenone may increase levels
||C - Safety for use during pregnancy
has not been established.
||Caution in CHF being treated with
digitalis, diuretics, or ACE inhibitors (AV conduction may be
slowed); discontinue if liver impairment occurs; caution in
peripheral vascular disease (at higher doses) and
||Section 8 of 10 |
Further Inpatient Care:
- After the patient has been initially stabilized and the
decompensation of heart failure has been resolved, further inpatient
care depends on the underlying cause of CHF.
- Place patients with heart failure in a monitored bed to watch for
acute dysrhythmias. Pay strict attention to the patient's fluid balance
by closely monitoring fluid input and output. Maintain patients who are
fluid-overloaded in negative fluid balance through the use of diuretics,
or, if necessary in patients with renal failure, hemodialysis with
- Check cardiac enzymes to evaluate for myocardial infarction. Slight
elevations in cardiac enzymes can occur with decompensated heart failure
in the absence of myocardial infarction because of coronary thrombosis.
- Perform coronary angiography on patients whose decompensated heart
failure resulted from an acute coronary syndrome, either unstable angina
or myocardial infarction. Stress testing can also be performed later
during hospitalization to evaluate for reversible ischemia in patients
without acute coronary syndromes but who have prior symptoms of angina
or who have a high likelihood of coronary artery disease as the cause of
- Order echocardiography at the earliest possible moment to evaluate
for evidence of acute valvular dysfunction and wall motion abnormalities
and to assess the patient's systolic and diastolic function. Since the
long-term therapy of patients with heart failure differs significantly
between those with predominantly systolic dysfunction and those with
predominantly diastolic dysfunction, it is absolutely essential that all
patients with heart failure have echocardiographic evaluation of cardiac
function, chamber size, and valve function.
- In most patients with decompensated heart failure, oral vasodilator
therapy, most commonly ACE inhibitors, can be used as first-line therapy
to reverse the cardiac decompensation and to restore optimal cardiac
function. The clinician must be extremely cautious with vasodilator
therapy only in patients with severe aortic or mitral stenosis or in
those with obstructive cardiomyopathy. Patients who required intravenous
inotropic support should be weaned off as quickly as possible and should
have their vasodilator therapy maximized quickly in order to avoid the
risk of adverse cardiac events from increased myocardial oxygen
consumption leading to ischemia.
- Patients in whom pulmonary edema was caused by dietary factors or
medication noncompliance need strict counseling and education to help
Further Outpatient Care:
- Focus further outpatient care of patients with heart failure on
maximizing some or all of the medical modalities used in their
treatment. Undertake further assessment of the clinical and hemodynamic
effects of that therapy fairly soon after discharge and at regular
- Precise definition and aggressive treatment of all reversible causes
for heart failure is absolutely essential. For instance, patients with
myocardial ischemia (particularly those with reduced systolic function)
should be promptly evaluated with noninvasive and/or invasive
evaluations of coronary perfusion, and they should be promptly referred
for revascularization if they are suitable candidates for such
revascularization. Similarly, patients with severe valvular disease,
assessed clinically and echocardiographically, should be promptly
referred for cardiac catheterization. If a patient is a suitable
candidate for valve replacement or repair, he or she should undergo
prompt surgical therapy.
- Patients with nonreversible NYHA class IV heart failure who are
younger than 65 years and facing the likely prospect of death within the
next 6-24 months, despite maximal medical therapy, and who are not
candidates for beneficial surgical therapy, should be promptly referred
to a cardiac transplant center for consideration of cardiac
- Screen patients with cardiomyopathy and heart failure for candidacy
for cardioverter/defibrillator implantation because the risk of sudden
death in these patients is considerable.
In/Out Patient Meds:
- Transfer of patients to a tertiary receiving hospital generally is
indicated if the presenting hospital lacks adequate resources to care
for such patients. Most patients with heart failure can be well managed
at community hospitals. However, if the cause of heart failure is
determined to require definitive surgery for stabilization, transfer is
often indicated. Note the following examples:
- Patients with heart failure that develops as a result of acute
valvular dysfunction requiring urgent valve replacement may require
transfer to a tertiary care facility that performs open heart
- Patients with acute myocardial infarction resulting in cardiogenic
shock hypotension may require transfer for emergency PTCA or CABGS.
Thrombolysis may be attempted at the presenting hospital, but outcome
is generally poor without angioplasty or CABGS.
- Patients with severe heart failure with hemodynamic complications
should be transferred from presenting hospitals that lack sufficient
resources for, or experience with, managing patients with heart
failure who require complex inotropic support or
- Patients with NYHA class IV heart failure who are younger than 65
years and facing the likely prospect of death within the next 6-12
months, despite maximal medical therapy, and who are not candidates
for coronary revascularization, should be transferred to a cardiac
transplant center for consideration of cardiac transplantation if they
cannot be stabilized enough to be discharged home on maximal medical
and mechanical therapy.
- The major complications associated with heart failure are sudden
cardiac death from ventricular tachyarrhythmias or bradyarrhythmias and
pump failure with cardiovascular collapse. Approximately half of
patients with heart failure eventually die from fatal ventricular
arrhythmias. Prompt diagnosis and treatment usually prevent this
complication in the acute setting. Prompt diagnosis of CHF and prompt
treatment to reduce pulmonary venous congestion, reduce afterload, and
improve cardiac output is essential in preventing cardiovascular and
- In general, the inpatient mortality rate for patients with heart
failure is 5-20%.
- Heart failure associated with acute myocardial infarction is
associated with an inpatient mortality rate of 20-40%; mortality
approaches 80% in patients who are also hypotensive (eg, cardiogenic
- To help prevent recurrence, counsel and educate patients in whom
heart failure was caused by dietary factors or medication noncompliance
with regard to the importance of proper diet and the necessity of
||Section 9 of 10 |
- Failure to rapidly recognize decompensated heart failure and to
distinguish this entity from other pulmonary diseases
- Failure to rapidly initiate medical therapy for heart
- Failure to rapidly diagnose and treat acute coronary syndromes that
cause heart failure
- Failure to rapidly and aggressively treat cardiac arrhythmias that
may cause or result from heart failure
- Failure to rapidly and aggressively treat the hypoxia and acidosis
that results from acute severe heart failure with mechanical
- Failure to provide rapid and aggressive hemodynamic support and to
use, when clinically indicated, invasive hemodynamic monitoring in an
effective and diagnostically sound manner
- Consider peripartum cardiomyopathy in women presenting with symptoms
suggestive of heart failure in the peripartum period.
||Section 10 of
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