Heart Failure and Cor Pulmonale

Heart Failure

Definition

Heart failure (HF) is a clinical syndrome that occurs in

patients who, because of an inherited or acquired
abnormality of cardiac structure and/or function,
develop a constellation of clinical symptoms (dyspnea
and fatigue) and signs (edema and rales) that lead to
frequent hospitalizations, a poor quality of life, and a
shortened life expectancy.

Epidemiology
The overall prevalence of HF in the adult population in
developed countries is 2%.
Rising with age, and affects 6–10% of people over age 65.
The lifetime risk of developing HF is approximately one in
five for a 40-year-old.
HF patients are now broadly categorized into one of two
groups:
(1) HF with a depressed EFor
(2) HF with a preserved EF (EF 40-50%).

Etiology

In industrialized countries,
coronary artery disease (60–75%) of cases of HF.
Hypertension 75% of patients

Etiologies of Heart Failure

Depressed Ejection Fraction (<40%)
Coronary artery disease
Nonischemic dilated cardiomyopathy
Chronic pressure overload
Toxic/drug-induced damage
Chronic volume overload
Chagas' disease
Preserved Ejection Fraction (>40–50%)
Pathologic hypertrophy
Restrictive cardiomyopathy
Aging Fibrosis
Endomyocardial disorders

Pulmonary Heart Disease

Cor pulmonale
Pulmonary vascular disorders
High-Output States
Excessive blood-flow requirements
Thyrotoxicosis
Systemic arteriovenous shunting
Nutritional disorders (beriberi)
Chronic anemia

In 20–30% of the cases of HF with a depressed EF, the

exact etiologic basis is not known.
Conditions that lead to a high cardiac output (e.g.,
arteriovenous fistula, anemia) are seldom responsible for
the development of HF in a normal heart; however, in
the presence of underlying structural heart disease,
these conditions can lead to overt HF.

Global Considerations
Rheumatic heart disease remains a major cause of HF in
Africa and Asia, especially in the young.
Hypertension is an important cause of HF in the African
and African-American populations.
Chagas' disease is still a major cause of HF in South
America.
Diabetes accelerates atherosclerosis and often is
associated with hypertension.

Prognosis
The development of symptomatic HF still carries a poor
prognosis. 30–40% of patients die within 1 year of
diagnosis and 60–70% die within 5 years
Patients with symptoms at rest [class IV] have a 30–70%
annual mortality rate

New York Heart Association Classification

Functional Capacity - Objective Assessment
Class I- Patients with cardiac disease but without
resulting limitation of physical activity. Ordinary physical
activity does not cause undue fatigue, palpitations,
dyspnea, or anginal pain.
Class II- Patients with cardiac disease resulting in slight
limitation of physical activity. They are comfortable at
rest. Ordinary physical activity results in fatigue,
palpitation, dyspnea, or anginal pain.
Class III- Patients with cardiac disease resulting in
marked limitation of physical activity. They are
comfortable at rest. Less than ordinary activity causes
fatigue, palpitation, dyspnea, or anginal pain.
Class IV- Patients with cardiac disease resulting in
inability to carry on any physical activity without
discomfort. Symptoms of heart failure or the anginal
syndrome may be present even at rest. If any physical
activity is undertaken, discomfort is increased.

Pathogenesis
HF 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 (MI); it may
have a gradual or insidious onset; or it may be
hereditary, as in the case of many of the genetic
cardiomyopathies.

After initial decline in pumping capacity, a variety of

compensatory mechanisms are activated, including the
adrenergic nervous system, the renin-angiotensin-
aldosterone system, and the cytokine system. In the
short term, these systems are able to restore
cardiovascular function to a normal homeostatic range
with the result that the patient remains asymptomatic.
However, with time the sustained activation of these
systems can lead to secondary end-organ damage within
the ventricle, with worsening left ventricular remodeling
and subsequent cardiac decompensation.
compensatory mechanisms are responsible for
maintaining cardiac output through increased retention
of salt and water and (2) increased myocardial
contractility.

Mechanisms that contribute to the development of HF

with a preserved EF is still evolving.
Diastolic dysfunction
Increased vascular stiffness and
Impaired renal function.

Basic Mechanisms of Heart Failure

Systolic Dysfunction

LV remodeling develops
(1) myocyte hypertrophy,
(2) alterations in the contractile properties of the
myocyte,
(3) progressive loss of myocytes through necrosis,
apoptosis, and autophagic cell death,
(4) -adrenergic desensitization,
(5) abnormal myocardial energetics and metabolism,
and
(6) reorganization of the extracellular matrix

The biologic stimuli for these profound changes include

mechanical stretch of the myocyte, circulating
neurohormones, inflammatory cytokines [e.g., tumor
necrosis factor (TNF)], other peptides and growth factors
(e.g., endothelin), and reactive oxygen species (e.g.,
superoxide).
Diastolic Dysfunction

Reductions in ATP concentration, as occurs in ischemia,

lead to slowed myocardial relaxation.
An increase in heart rate disproportionately shortens the
time for diastolic filling, which may lead to elevated LV
filling pressures, particularly in noncompliant ventricles.
Elevated LV end-diastolic filling pressures result in
increases in pulmonary capillary pressures, which can
contribute to the dyspnea experienced by patients with
diastolic dysfunction.

increased myocardial stiffness secondary to cardiac

hypertrophy and increased myocardial collagen content
may contribute to diastolic failure.
Left Ventricular Remodeling

Ventricular remodeling refers to the changes in LV mass,

volume, and shape and the composition of the heart that
occur after cardiac injury and/or abnormal hemodynamic
loading conditions
Clinical Manifestations

Symptoms

The cardinal symptoms of HF are fatigue and shortness

of breath.
In the early stages of HF, dyspnea is observed only during
exertion; however, as the disease progresses, dyspnea
occurs with less strenuous activity, and it ultimately may
occur even at rest.
The most important mechanism is pulmonary
congestion, shallow breathing characteristic of cardiac
dyspnea.
Other factors that contribute to dyspnea on exertion
include reductions in pulmonary compliance, increased
airway resistance, respiratory muscle and/or diaphragm
fatigue, and anemia.
Dyspnea may become less frequent with the onset of
right ventricular (RV) failure and tricuspid regurgitation.

Orthopnea

Dyspnea occurring in the recumbent position.

It results from redistribution of fluid from the splanchnic
circulation and lower extremities into the central
circulation during recumbency, with a resultant increase
in pulmonary capillary pressure. Nocturnal cough is a
common manifestation of this process and a frequently
overlooked symptom of HF. relieved by sitting upright or
sleeping with additional pillows.
DDx,abdominal obesity or ascites and patients with
pulmonary disease
Paroxysmal Nocturnal Dyspnea (PND)
Acute episodes of severe shortness of breath and
coughing that generally occur at night and awaken the
patient from sleep, usually 1–3 hours after the patient
retires. may be manifest by coughing or wheezing.
patients with PND often have persistent coughing and
wheezing even after they have assumed the upright
position.
Cheyne-Stokes Respiration

Also referred to as periodic respiration or cyclic

respiration, present in 40% of patients with advanced HF
and usually is associated with low cardiac output.
caused by a diminished sensitivity of the respiratory
center to arterial Pco2. There is an apneic phase, during
which arterial Po2 falls and arterial Pco2 rises.

Acute Pulmonary Edema

usually presents with the rapid onset of dyspnea at rest,
tachypnea, tachycardia, and severe hypoxemia.
Rales and wheezing due to airway compression from
peribronchial cuffing may be audible. Hypertension is
usually present due to release of endogenous
catecholamines.
Brain natriuretic peptide levels, when substantially
elevated, support heart failure as the etiology of acute
dyspnea with pulmonary edema.

Other Symptoms

Patients with HF also may present with gastrointestinal

symptoms. Anorexia, nausea, and early satiety associated
with abdominal pain and fullness are common
complaints and may be related to edema of the bowel
wall and/or a congested liver.
right-upper-quadrant pain.
Cerebral symptoms such as confusion, disorientation,
and sleep and mood disturbances
Nocturia is common in HF and may contribute to
insomnia.
Physical Examination

to help determine the cause of HF as well as to assess the

severity of the syndrome.
General Appearance and Vital Signs
In more severe HF, the patient must sit upright, may
have labored breathing, and may not be able to finish a
sentence because of shortness of breath.
The pulse pressure may be diminished, reflecting a
reduction in stroke volume.
Peripheral vasoconstriction leading to cool peripheral
extremities and cyanosis of the lips and nail beds is also
caused by excessive adrenergic activity.

Jugular Veins

provides an estimation of right atrial pressure.

Giant v waves indicate the presence of tricuspid
regurgitation.

Pulmonary Examination

Pulmonary crackles (rales or crepitations) result from the

transudation of fluid from the intravascular space into
the alveoli.
Pleural effusions result from the elevation of pleural
capillary pressure and the resulting transudation of fluid
into the pleural cavities. often bilateral in HF, when they
are unilateral, they occur more frequently in the right
pleural space.

Cardiac Examination
If cardiomegaly is present, the point of maximal impulse
(PMI) usually is displaced below the fifth intercostal
space and/or lateral to the midclavicular line, and the
impulse is palpable over two interspaces.
In some patients, a third heart sound (S3) is audible and
palpable at the apex.
The murmurs of mitral and tricuspid regurgitation are
frequently present in patients with advanced HF.

Abdomen and Extremities

Hepatomegaly is an important sign in patients with HF.

may pulsate during systole if tricuspid regurgitation is
present. Ascites, Jaundice, a late finding in HF
Peripheral edema is a cardinal manifestation of HF, but it
is nonspecific and usually is absent in patients who have
been treated adequately with diuretics.
Peripheral edema is usually symmetric and dependent in
HF
Long-standing edema may be associated with indurated
and pigmented skin.

Cardiac Cachexia

With severe chronic HF, there may be marked weight

loss and cachexia. Although the mechanism of cachexia is
not entirely understood, it is probably multifactorial and
includes elevation of the resting metabolic rate;
anorexia, nausea, and vomiting due to congestive
hepatomegaly and abdominal fullness; elevation of
circulating concentrations of cytokines such as TNF; and
impairment of intestinal absorption due to congestion of
the intestinal veins. When present, cachexia augurs a
poor overall prognosis.

Diagnosis
classic signs and symptoms of HF
high index of suspicion, particularly for high-risk
patients. When these patients present with signs or
symptoms of HF, additional laboratory testing should be
performed.

Routine Laboratory Testing

complete blood count, a panel of electrolytes, blood urea

nitrogen, serum creatinine, hepatic enzymes, and a
urinalysis. Selected patients should have assessment for
diabetes mellitus, dyslipidemia, and thyroid
abnormalities.

Electrocardiogram (ECG)
to assess cardiac rhythm and determine the presence of
LV hypertrophy or a prior
A normal ECG virtually excludes LV systolic dysfunction.

Chest X-Ray

useful information about cardiac size and shape, as well

as the state of the pulmonary vasculature, and may
identify noncardiac causes of the patient's symptoms.

Assessment of Lv Function

Biomarkers
Circulating levels of natriuretic peptides are useful
adjunctive tools in the diagnosis of patients with HF.
Other biomarkers, such as troponin T and I, C-reactive
protein, TNF receptors, and uric acid, may be elevated in
HF and provide important prognostic information.
Exercise Testing

Treadmill or bicycle exercise testing is not routinely

advocated for patients with HF, but either is useful for
assessing the need for cardiac transplantation in patients
with advanced HF
Differential Diagnosis

renal failure and (2) noncardiac causes of pulmonary

edema (e.g., acute respiratory distress syndrome

A very low BNP or N-terminal pro-BNP may be helpful in

excluding a cardiac cause of dyspnea in this setting.
Ankle edema may arise secondary to varicose veins,
obesity, renal disease, or gravitational effects.
Treatment: Heart Failure

Depend on stages.
Stage A includes patients who are at high risk for
developing HF but do not have structural heart disease or
symptoms of HF (e.g., patients with diabetes mellitus or
hypertension).
Stage B includes patients who have structural heart
disease but do not have symptoms of HF (e.g., patients
with a previous MI and asymptomatic LV dysfunction).
Stage C includes patients who have structural heart
disease and have developed symptoms of HF (e.g.,
patients with a previous MI with dyspnea and fatigue).
Stage D includes patients with refractory HF requiring
special interventions (e.g., patients with refractory HF
who are awaiting cardiac transplantation).
every effort should be made to prevent HF not only by
treating the preventable causes of HF (e.g.,
hypertension) but also by treating the patient in stages B
and C with drugs that prevent disease progression (e.g.,
ACE inhibitors and beta blockers) and by symptomatic
management of patients in stage D.

Defining an Appropriate Therapeutic Strategy for

Chronic HF
Management of HF with Depressed Ejection Fraction
(<40%)

General Measures

screen for and treat comorbidities such as hypertension,

CAD, diabetes mellitus, anemia, and sleep-disordered
breathing, as these conditions tend to exacerbate HF.
should be advised to stop smoking and to limit alcohol
consumption to two standard drinks per day in men or
one per day in women.
abstain from alcohol consumption indefinitely.
 Extremes of temperature and heavy physical exertion
should be avoided. Certain drugs are known to make HF
worse and should be avoided. For example, nonsteroidal
anti-inflammatory drugs, because the risk of renal failure
and fluid retention is markedly increased in the presence
of reduced renal function or ACE inhibitor therapy.
Factors That May Precipitate Acute Decompensation in
Patients with Chronic Heart Failure
Dietary indiscretion
Myocardial ischemia/infarction
Arrhythmias (tachycardia or bradycardia)
Discontinuation of HF therapy
Infection
Anemia
Initiation of medications that worsen HF
Calcium antagonists (verapamil, diltiazem)
Beta blockers
Nonsteroidal anti-inflammatory drugs
 Antiarrhythmic agents [all class I agents, sotalol (class
III)]
Anti-TNF antibodies
Alcohol consumption
Pregnancy
Worsening hypertension
Acute valvular insufficiency

Activity

routine modest exercise has been shown to be beneficial

in patients with NYHA class I–III HF. Exercise training
results in reduced HF symptoms, increased exercise
capacity, and improved quality of life.

Diet
Dietary restriction of sodium (2–3 g daily) is
recommended in all patients with HF and preserved or
depressed EF.
Caloric supplementation is recommended for patients
with advanced HF and unintentional weight loss or
muscle wasting (cardiac cachexia
Diuretics

Many of the clinical manifestations of moderate to

severe HF result from excessive salt and water retention
that leads to volume expansion and congestive
symptoms. Diuretics are the only pharmacologic agents
that can adequately control fluid retention in advanced
HF, and they should be used to restore and maintain
normal volume status in patients with congestive
symptoms (dyspnea, orthopnea, edema) or signs of
elevated filling pressures (rales, jugular venous
distention, peripheral edema).
Preventing Disease Progression
ACE inhibitors and beta blockers
ACE Inhibitors
There is overwhelming evidence that ACE inhibitors
should be used in symptomatic and asymptomatic
patients with a depressed EF (<40%).

Cor Pulmonale
Definition

Cor pulmonale, often referred to as pulmonary heart

disease, is defined as dilation and hypertrophy of the
right ventricle in response to diseases of the pulmonary
vasculature and/or lung parenchyma.
Etiology and Epidemiology

Cor pulmonale develops in response to acute or chronic

changes in the pulmonary vasculature and/or the lung
parenchyma that are sufficient to cause pulmonary
hypertension.
Although COPD and chronic bronchitis are responsible
for approximately 50% of the cases of cor pulmonale in,
any disease that affects the pulmonary vasculature or
parenchyma can lead to cor pulmonale.

Etiology of Chronic Cor Pulmonale

Diseases Leading to Hypoxemic Vasoconstriction
Chronic bronchitis
Chronic obstructive pulmonary disease
Cystic fibrosis
Chronic hypoventilation
Obesity
Neuromuscular disease
Chest wall dysfunction
Living at high altitudes
Diseases that Cause Occlusion of the Pulmonary
Vascular Bed
Thromboembolic disease, acute or chronic
Pulmonary arterial hypertension
Pulmonary veno-occlusive disease

Diseases that Lead to Parenchymal Disease

Chronic bronchitis
Chronic obstructive pulmonary disease
Bronchiectasis
Cystic fibrosis
Pneumoconiosis
Sarcoidosis
Interstitial lung disease

Pathophysiology and Basic Mechanisms

the common pathophysiologic mechanism in each case is

pulmonary hypertension that is sufficient to lead to RV
dilation, with or without the development of
concomitant RV hypertrophy. The systemic
consequences of cor pulmonale relate to alterations in
cardiac output as well as salt and water homeostasis.
The response of the RV to pulmonary hypertension
depends on the acuteness and severity of the pressure
overload. Acute cor pulmonale occurs after a sudden and
severe stimulus (e.g., massive pulmonary embolus), with
RV dilatation and failure but no RV hypertrophy.
Chronic cor pulmonale, however, is associated with a
more slowly evolving and progressive pulmonary
hypertension that leads to initial modest RV hypertrophy
and subsequent RV dilation.
RV failure also can be precipitated by alterations in RV
volume that occur in various settings, including increased
salt and fluid retention, atrial arrhythmias, polycythemia,
sepsis, and a large left-to-right shunt.
The most common mechanisms that lead to pulmonary
hypertension, including vasoconstriction, activation of
the clotting cascade, and obliteration of pulmonary
arterial vessels.

Clinical Manifestations
Symptoms
The symptoms of chronic cor pulmonale generally are
related to the underlying pulmonary disorder. Dyspnea.
Orthopnea and paroxysmal nocturnal dyspnea are rarely
symptoms of isolated right HF and usually point toward
concurrent left heart dysfunction.
Abdominal pain and ascites that occur with cor
pulmonale are similar to the right-heart failure that
ensues in chronic HF. Lower-extremity edema may occur
secondary to neurohormonal activation
Signs
Many of the signs encountered in cor pulmonale are also
present in HF patients with a depressed EF, including
tachypnea, elevated jugular venous pressures,
hepatomegaly, and lower-extremity edema.

RV heave palpable along the left sternal border or in the

epigastrium.
The increase in intensity of the holosystolic murmur of
tricuspid regurgitation with inspiration ("Carvallo's sign")
may be lost eventually as RV failure worsens.
Cyanosis is a late finding in cor pulmonale and is
secondary to a low cardiac output with systemic
vasoconstriction and ventilation-perfusion mismatches in
the lung.

Diagnosis
evaluate the patient for LV systolic and diastolic
dysfunction.
ECG
Radiographic examination of the chest may show
enlargement of the main pulmonary artery, the hilar
vessels, and the descending right pulmonary artery.
Spirometry
arterial blood gases can demonstrate hypoxemia and/or
hypercapnia.
CT scans of the chest are useful in diagnosing acute
thromboembolic disease
echocardiography is useful for measuring RV thickness
and chamber dimensions as well as the anatomy of the
pulmonary and tricuspid valves.
BNP and N-terminal BNP levels are elevated in patients
with cor pulmonale secondary to RV stretch and may be
dramatically elevated in acute pulmonary embolism.

Treatment: Cor Pulmonale

The primary treatment goal of cor pulmonale is to target

the underlying pulmonary disease
General principles of treatment include decreasing work
of breathing by using noninvasive mechanical ventilation
and bronchodilation, as well as treating any underlying
infection

Adequate oxygenation (oxygen saturation 90–92%) and

correcting respiratory acidosis are vital for decreasing
pulmonary vascular resistance and reducing demands on
the RV.
Miesso(MD)