Heart Failure
1. Definition
HF is a complex clinical syndrome that
results from any structural or functional
impairment of ventricular filling or
ejection of blood. Acute Heart Failure
can be defined as the new onset or
recurrence of symtomps and signs of
heart failure requiring urgent or
emergent therapy and resulting in
seeking unscheduled care or
hospitalization. There is no widely
accepted nomenclature for HF
syndromes requiring hospitalization.
Patients are described as having “acute
HF,” “acute HF syndromes,” or
“acute(ly) decompensated HF”; while
the third has gained greatest acceptance,
it too has limitations, for it does not
make the important distinction between
those with a de novo presentation of HF
from those with worsening of
previously chronic stable HF. Because
some patients present without signs or
symptoms of volume overload, the term
“heart failure” is preferred over
“congestive heart failure”.
Most patients with HF have symptoms
due to impaired left ventricular
myocardial function. It should be
emphasized that HF is not synonymus
with either cardiomyopathy or LV
dysfunction; these latter terms describe
possible structural or functional reasons
for the development of HF; HF may be
associated with a wide spectrum of LV
functional abnormalities, which may
range from patients with normal LV
size and preserved EF to those with
severe dilatation and/or markedly
reduced EF. EF is considered important
in classification of patients with HF
because of differing patient
demographics, comorbid conditions,
prognosis, and response to therapies
and because most clinical trials selected
patients based on EF, it is preferable to
use the terms preserved or reduced EF
over preserved (HFpEF) or reduced
systolic function (HFrEF).
a. HF with Reduced EF (HFrEF)
HFrEF is defined as the clinical
diagnosis of HF and EF ≤40%. In
approximately half of patients with
HFrEF, variable degrees of LV
enlargement may accompany HFrEF.
Those with LV systolic dysfunction
commonly have elements of diastolic
dysfunction as well.
b. HF with Preserved EF (HFpEF)
Because some of these patients do not
have entirely normal EF but also do not
have major reduction in systolic
function, the term preserved EF has
been used. Patients with an EF in the
range of 40% to 50% represent an
intermediate group. In the general
population, patients with HFpEF are
usually older women with a history of
hypertension. Obesity, CAD, diabetes
mellitus, atrial fibrillation (AF), and
hyperlipidemia are also highly
prevalent in HFpEF in population-
based studies and registries. Despite
these associated cardiovascular risk
factors, hypertension remains the most
important cause of HFpEF, with a
prevalence of 60% to 89% from large
controlled trials, epidemiological
studies, and HF registries.
2. Classification
The ACCF/AHA stages of HF
emphasize the development and
progression of disease and can be used
to describe individuals and populations,
whereas the NYHA classes focus on
exercise capacity and the symptomatic
status of the disease.
3. Epidemiology
The lifetime risk of developing HF is
20% for Americans ≥40 years of age.
HF incidence increases with age, rising
from approximately 20 per 1000
individuals 65 to 69 years of age to >80
per 1000 individuals among those ≥85
years of age. Although survival has
improved, the absolute mortality rates
for HF remain approximately 50%
within 5 years of diagnosis. In the ARIC
(Atherosclerosis Risk in Communities)
study, the 30-day, 1-year, and 5-year
case fatality rates after hospitalization
for HF were 10.4%, 22%, and 42.3%,
respectively.
4. Patophysiology
Heart failure may be viewed as a
progressive disorder that is initiated
after an index event either damages the
heart muscle, with a resultant loss of
functioning cardiac myocytes or,
alternatively, disrupts the ability of the
myocardium to generate force, thereby
preventing the heart from contracting
normally. This index event may have an
abrupt onset, as in the case of a
myocardial infarction; it may have a
gradual or insidious onset, as in the case
of hemodynamic pressure or volume
overloading.
Regardless of the nature of the inciting
event, the feature that is common to
each of these index events is that they
all, in some manner, produce a decline
in pumping capacity of the heart. In
most instances, patients will remain
asymptomatic or minimally
symptomatic after the initial decline in
pumping capacity of the heart, or
symptoms develop only after the
dysfunction has been present for some
time. Although the precise reasons why
patients with LV dysfunction remain
asymptomatic have not been
established with certainty, one potential
explanation is that a number of
compensatory mechanisms that become
activated in the setting of cardiac injury
or depressed cardiac output appear to
modulate LV function within a
physiologic/homeostatic range.
With progression to symptomatic heart
failure, however, the sustained
activation of neurohormonal and
cytokine systems leads to a series of
end-organ changes within the
myocardium referred to collectively as
LV remodeling. As discussed further
on, LV remodeling is sufficient to lead
to disease progression in heart failure
independent of the neurohormonal
status of the patient.
a. Sympathetic Nervous System
The decrease in cardiac output in heart
failure activates a series of
compensatory adaptations that are
intended to maintain cardiovascular
homeostasis. One of the most
important adaptations is activation of
the sympathetic (adrenergic) nervous
system, which occurs early in the
course of heart failure. Healthy persons
display low sympathetic discharge at
rest and have a high heart rate
variability. In patients with heart
failure, however, inhibitory input from
baroreceptors and mechanoreceptors
decreases and excitatory input
increases, with the net result of a
generalized increase in sympathetic
nerve traffic and blunted
parasympathetic nerve traffic, leading
to loss of heart rate variability and
increased peripheral vascular
resistance.
Moreover, increasing evidence
suggests that apart from the deleterious
effects of sympathetic activation,
parasympathetic withdrawal also may
contribute to the pathogenesis of heart
failure. Withdrawal of parasympathetic
nerve stimulation has been associated
with decreased nitric oxide (NO)
levels, increased inflammation,
increased sympathetic activity and
worsening LV remodeling.
b. Renin-Angiotensin System
In contrast with the sympathetic
nervous system, the components of the
RAS are activated comparatively later
in heart failure. The presumptive
mechanisms for RAS activation in
heart failure include renal
hypoperfusion, decreased filtered
sodium reaching the macula densa in
the distal tubule, and increased
sympathetic stimulation of the kidney,
leading to increased renin release from
jutaglomerular apparatus. Angiotensin
II has several important actions that are
critical to maintaining short-term
circulatory homeostasis.
The sustained expression of
angiotensin II is maladaptive, however,
leading to fibrosis of the heart, kidneys,
and other organs. Angiotensin II can
also lead to worsening neurohormonal
activation by enhancing the release of
NE from sympathetic nerve endings, as
well as stimulating the zona
glomerulosa of the adrenal cortex to
produce aldosterone. Analogous to
angiotensin II, aldosterone provides
shortterm support to the circulation by
promoting the reabsorption of sodium
in exchange for potassium, in the distal
segments of the nephron. However, the
sustained expression of aldosterone
may exert harmful effects by
provoking hypertrophy and fibrosis
within the vasculature and the
myocardium, contributing to reduced
vascular compliance and increased
ventricular stiffness.
5. LV Remodeling with or without LV wall thinning. The
myocytes from these failing ventricles
Although neurohormonal antagonists
have an elongated appearance that is
stabilize and in some cases reverse
characteristic of myocytes obtained
certain aspects of the disease process in
from hearts subjected to chronic
heart failure, in the overwhelming
volume overload.
majority of patients, it will progress,
albeit at a slower rate. It has been 6. Symptoms
suggested that the process of LV
Worsening dyspnea is a cardinal
remodeling is directly related to future
symptom of HF and typically is related
deterioration in LV performance and a
to increases in cardiac filling pressures
less favorable clinical course in patients
but also may represent restricted cardiac
with heart failure. The process of LV
output.3 The absence of worsening
remodeling also has an important
dyspnea, however, does not necessarily
impact on the biology of the cardiac
exclude the diagnosis of HF, because
myocyte, on changes in the volume of
patients may accommodate symptoms
myocyte and nonmyocyte components
by substantially modifying their
of the myocardium, and on the
lifestyle. Patients may sleep with the
geometry and architecture of the LV
head elevated to relieve dyspnea while
chamber.
recumbent (orthopnea); additionally,
Two basic patterns of cardiac dyspnea may occur specifically in
hypertrophy occur in response to recumbency on the left side
hemodyamic overload. In pressure (trepopnea). Paroxysmal nocturnal
overload hypertrophy (e.g., with aortic dyspnea, shortness of breath developing
stenosis or hypertension), the increase in recumbency, is one of the most
in systolic wall leads to the addition of highly reliable indicators of HF.
sarcomeres in parallel, an increase in
These symptoms all typically reflect
myocyte cross-sectional area, and
pulmonary congestion, whereas a
increased LV wall thickening. This
history of weight gain, increasing
pattern of remodeling has been referred
abdominal girth, early satiety, and the
to as “concentric” hypertrophy. By
onset of edema in dependent organs
contrast, in volume overload
(extremities or scrotum) indicate right
hypertrophy (e.g., with aortic and
heart congestion; nonspecific, right
mitral regurgitation), increased
upper quadrant pain due to congestion
diastolic wall stress leads an increase in
of the liver is common in those with
myocyte length with the addition of
significant right-sided HF and may be
sarcomeres in series, thereby
incorrectly attributed to other
engendering increased LV ventricular
conditions. The presence of
dilation). This pattern of remodeling
hypertension, coronary artery disease
has been referred to as “eccentric”
and/or diabetes is particularly helpful
hypertrophy.
since these conditions account for
Patients with heart failure classically approximately 90% of the population
present with a dilated left ventricle attributable risk for HF in the United
States. Although most disorders
causing HF are cardiac, it is worth
remembering that some systemic
illnesses (e.g., anemia,
hyperthyroidism) can cause this
syndrome without direct cardiac
involvement.
7. Physical Findings
No physical finding in HF is absolutely
pathognomonic for HFpEF versus
HFrEF. An evaluation for the presence
and severity of HF should include
consideration of the patient’s general
appearance, measurement of vital signs
in the seated and standing positions,
examination of the heart and pulses, and
assessment of other organs for evidence
of congestion or hypoperfusion or
indications of comorbid conditions. The
details of inspection and palpation of
the heart are discussed in Chapter 11.
By observing or palpating the apical
impulse, the examiner can rapidly
determine heart size and quality of the
point of maximal impulse. In cases of
severe HF, a palpable third heard sound
may be present.
Cardiac auscultation (Chapter 11) is a
crucial part of HF evaluation. The
presence of a third heart sound is a
crucially important finding and
suggests increased ventricular filling
volume; although difficult to identify, a
third heart sound is highly specific for
HF and carries a substantial prognostic
meaning. A fourth heart side usually
indicates ventricular stiffening. A key
objective of the examination in patients
with HF is to detect and quantify the
presence of volume retention, with or
without pulmonary and/or systemic
congestion. The most definitive method
for assessing a patient’s volume status
by physical examination is by the
measurement of jugular venous
pressure (JVP), which is discussed in
detail in Chapter 11. An elevated JVP
has good sensitivity (70%) and
specificity (79%) for elevated left-sided
filling pressure.
Although pulmonary congestion is
exceedingly common in HF, physical
findings indicating its presence are
variable, and many are nonspecific.
Leakage of fluid from pulmonary
capillaries into the alveoli can be
manifested as rales or rhonchi, and
wheezing may occur with reactive
bronchoconstriction. Pulmonary rales
due to HF usually are fine in nature and
extend from the base upwards, whereas
those due to other causes (e.g.,
pulmonary fibrosis) tend to be coarser.
Lower-extremity edema is a common
finding in volume-overloaded patients
with HF but may commonly be the
result of venous insufficiency
(particularly after saphenous veins have
been harvested for coronary artery
bypass grafts) or as a side effect of
medications (e.g., calcium channel
blockers).
Assessment for systemic congestion,
taken together with evaluation for
reduced cardiac output, may be useful
to separate patients with HF (Fig. 23-2)
into “dry/warm” (uncongested with
normal perfusion), “wet/warm”
(congested with normal perfusion, the
most common combination found in
decompensated HF), “dry/cold”
(uncongested but hypoperfused), and
“wet/cold” (cardiogenic shock)
categories.
8. Evaluation
a. Chest Radiography
The classic chest radiograph
appearance in patients with pulmonary
edema is a “butterfly” pattern of
interstitial and alveolar opacities
bilaterally fanning out to the periphery
of the lungs. Pleural effusions and/or
fluid in the right minor fissure also be
seen.
b. Electrocardiogram
Sinus tachycardia secondary to
sympathetic nervous system activation
is seen with advanced HF or during
episodes of acute decompensation. The
presence of increased QRS voltage
may suggest left ventricular
hypertrophy. Low QRS voltage
suggests the presence of an infiltrative
disease or pericardial effusion.
The presence of Q waves suggests that
HF may be due to ischemic heart
disease; new or reversible ST changes
identify acute coronary ischemia,
which may be present even when chest
pain is absent. Indeed, because acute
coronary ischemia is a leading cause of
acutely decompensated HF, a 12-lead
ECG should be immediately obtained
in this setting, in order to exclude acute
MI.
c. Natriuretic Peptide
Assays for BNP (B-type natriuretic
peptide) and NT-proBNP (N-terminal
pro-B-type natriuretic peptide), which
are both natriuretic peptide biomarkers,
have been used increasingly to
establish the presence and severity of
HF. In general, both natriuretic peptide
biomarker values track similarly, and
either can be used in patient care
settings as long as their respective
absolute values and cutpoints are not
used interchangeably.
d. Echocardiography
Transthoracic echocardiography is an
important part of the evaluation of HF,
can be performed without risk to the
patient, does not involve radiation
exposure, and can be performed at the
bedside if necessary. It is particularly
well suited for evaluating the structure
and function of both the myocardium factors for developing LV hypertrophy,
and heart valves and providing another form of stage B. Although the
information about intracardiac magnitude of benefit varies with the
pressures and flows. trial selection criteria, target blood
pressure reduction, and HF criteria,
9. Treatment
effective hypertension treatment
a. Stage A: Recommendation
invariably reduces HF events.
Recognition and treatment of elevated
Nevertheless, neither ACE inhibitors
blood pressure, which is a majorr risk
nor beta blockers as single therapies
factor for the development of both
are superior to other antihypertensive
HfrEF and HfpEF. Treatment of
drug classes, including calcium
dyslipidemia and vascular risk with
channel blockers, in the reduction of all
know arterosclerotic disease are likely
cardiovascular outcomes. However, in
to develop HF. Obesity and Diabetes
patients with type 2 diabetes mellitus,
mellitus have been repeatedly linked to
ACE inhibitors and ARBs significantly
an increase risk of HF.
reduced the incidence of HF in patients
b. Stage B: Recommendation
Diuretic-based antihypertensive
In general, all recommendations for therapy has been shown to prevent HF
patients with stage A HF also apply to in a wide range of target populations.
those with stage B HF, particularly In refractory hypertensive patients,
with respect to control of blood spironolactone (25 mg) should be
pressure in the patient with LV considered as an additional agent.
hypertrophy and the optimization of
lipids with statins. CAD is a major risk
factor for the development of HF and a
key target for prevention of HF. The 5-
year risk of developing HF after acute
MI is 7% and 12% for men and women,
respectively; for men and women
between the ages of 40 and 69 and
those >70 years of age, the risk is 22%
and 25%, respectively. Current
evidence supports the use of ACE
inhibitors and (to a lower level of
evidence) beta-blocker therapy to
impede maladaptive LV remodeling in
patients with stage B HF and low
LVEF to improve mortality and
morbidity. ARBs are reasonable
alternatives to ACE inhibitors.
Elevations in both systolic and
diastolic blood pressure are major risk
c. Stage C: Recommendation