Cardiomyopathies
Although descriptive rather than etiologic, the usual
designation of cardiomyopathy as hypertrophic, dilated, or restrictive has
provided a useful clinical and prognostic framework for diagnosis and
management (Table 1). Many infectious, metabolic, toxic, inflammatory, and
other causes have been implicated, but most patients who present with symptoms
or incidental abnormalities on routine cardiac evaluation in the absence of
significant systemic hypertension, valvular heart disease, or atherosclerotic
coronary artery disease have cardiomyopathies that have historically been
considered idiopathic (Fig. 59-1). However, most of these patients actually have
familial disease involving the sarcomere (hypertrophic cardiomyopathy), the
cytoskeleton (dilated cardiomyopathy), or cell adhesion (arrhythmogenic right
ventricular cardiomyopathy), although most family members have incomplete gene
expression and do not fulfill conventional clinical diagnostic criteria.
TABLE 1 -- HEMODYNAMIC TYPES OF MYOCARDIAL DISEASE
|
|
Hypertrophic |
Dilated |
Restrictive |
|
Causes |
Genetic (see Table 2) |
Myocarditis (see Table 5) |
Infiltrative
or storage diseases (see Table12) |
|
|
Secondary
to pressure overload (e.g., hypertension, aortic stenosis) |
Chronic (see Table 7) |
Endomyocardial (e.g., Löffler's, carcinoid) |
|
|
|
Genetic (see Table 59-3) |
|
|
|
|
Arrhythmogenic
right ventricular dysplasia (see Table 9) |
|
|
Ejection fraction (normal >55%) |
>60% |
<30% |
25–50% |
|
Left
ventricular diastolic dimension (normal < |
Often decreased |
≥60 mm |
< |
|
Left ventricular wall thickness |
Increased |
Decreased |
Normal or increased |
|
Atrial size |
Increased |
Increased |
Increased; may be massive |
|
Valvular regurgitation |
Mitral regurgitation |
Mitral
first during decompensation; tricuspid regurgitation in late stages |
Frequent
mitral and tricuspid regurgitation, rarely severe |
|
Common first symptoms[*] |
Exertional
intolerance; may have chest pain |
Exertional intolerance |
Exertional intolerance, fluid retention |
|
Congestive symptoms[*] |
Primary exertional dyspnea |
Left
before right, except right prominent in young adults |
Right often exceeds left |
|
Risk for arrhythmia |
Ventricular tachyarrhythmias, atrial
fibrillation |
Ventricular
tachyarrhythmias; atrial fibrillation; conduction block in Chagas' disease, giant
cell myocarditis, and some families |
Atrial
fibrillation; ventricular tachyarrhythmias uncommon except in sarcoidosis;
conduction block in sarcoidosis and amyloidosis |
|
* |
Left-sided symptoms of pulmonary congestion: dyspnea
on exertion, orthopnea, paroxysmal nocturnal dyspnea. Right-sided symptoms of
systemic venous congestion: discomfort on bending, hepatic and abdominal
distention, peripheral edema. |
|
|
|
|
FIGURE 1 Initial
approach to classification of cardiomyopathy.
The evaluation of symptoms or signs consistent with heart failure first
includes confirmation that they can be attributed to a cardiac cause.
Although this conclusion is often apparent from routine physical examination
and electrocardiography, echocardiography serves to confirm cardiac disease
and provides clues to the presence of other cardiac disease, such as focal
abnormalities, suggesting primary valve disease or congenital heart disease.
Having excluded these conditions, cardiomyopathy is generally considered to
be dilated, restrictive, or hypertrophic, as shown in Table 59-1. Patients
with apparently normal cardiac structure and contraction are occasionally
found to demonstrate abnormal intracardiac flow patterns consistent with
diastolic dysfunction but should also be evaluated carefully for other causes
of their symptoms. Most patients with so-called diastolic dysfunction also
demonstrate at least borderline criteria for left ventricular hypertrophy,
frequently in the setting of chronic hypertension and diabetes. A moderately
decreased ejection fraction without marked dilation or a pattern of
restrictive cardiomyopathy is sometimes referred to as “minimally dilated
cardiomyopathy,” which may represent either a distinct entity or a transition
between acute and chronic disease. |
|
Hypertrophic
Cardiomyopathy
Definition and Epidemiology
Hypertrophic cardiomyopathy is a genetically
determined myocardial disease, which is defined clinically by the presence of
unexplained left ventricular hypertrophy and pathologically by the presence of
myocyte disarray surrounding increased areas of loose connective tissue. The
disease occurs in all racial groups, with a prevalence of between 0.2 and 0.5%
in the general population, based on an unexplained left ventricular wall
thickness in excess of
Pathobiology
Genetics
Hypertrophic
cardiomyopathy is usually familial, with autosomal dominant inheritance.
Abnormalities in sarcomeric contractile protein genes (Table 2) account for
approximately 50 to 60% of cases. A similar clinical phenotype is seen in
association with several rare genetically determined disorders, including
Noonan's syndrome, Friedreich's ataxia, neurofibromatosis, hereditary
spherocytosis, aniridia with catalase deficiency, mitochondrial disease, and
several of the glycogen storage diseases (Table 3). The available
genotype/phenotype studies do not provide a ready explanation for the marked
clinical heterogeneity of hypertrophic cardiomyopathy. Studies of families in
whom disease-causing genes have been identified do, however, suggest that
different genes are associated with particular phenotypes, such as the
following: myosin-binding protein C, late-onset expression; troponin T,
premature sudden death; and troponin I, variable expression from generation to
generation (see later).
TABLE 2 -- FAMILIAL HYPERTROPHIC CARDIOMYOPATHY GENES, PROTEINS,
AND ESTIMATED FREQUENCY OF MUTATIONS IN PATIENTS WITH THE PHENOTYPE
|
Gene |
Protein |
Frequency |
|
MYH7 |
β-Myosin heavy chain |
25–35% |
|
MYBPC3 |
Cardiac
myosin binding protein C |
20–30% |
|
TNNT2 |
Cardiac troponin T |
3–5% |
|
TNNI3 |
Cardiac troponin I |
<5% |
|
TPM1 |
α-Tropomyosin |
<5% |
|
MYL2 |
Regulatory myosin light chain |
<5% |
|
MYL3 |
Essential myosin light chain |
Rare |
|
ACTC |
α-Cardiac actin |
Rare |
|
TTN |
Titin |
Rare |
|
TNNC1 |
Cardiac troponin C |
Rare |
|
MYH6 |
α-Myosin heavy chain |
Single study |
|
CRP3 |
Muscle LIM protein |
Rare |
TABLE 3 -- GENETIC CONDITIONS ASSOCIATED WITH PHENOTYPIC LEFT
VENTRICULAR HYPERTROPHY
|
Disorder |
Disease Gene |
|
|
METABOLIC DISEASE |
||
|
Glycogen storage diseases |
||
|
|
Pompe's disease |
GAA |
|
|
Forbes' disease |
AGL |
|
|
Danon's disease |
LAMP2 |
|
|
Wolff-Parkinson-White
syndrome, conduction disease |
PRKAG2 |
|
Fabry's disease |
GLA |
|
|
Mitochondrial
cytopathy (MELAS, MERRF, LHON) |
Various mitochondrial genes |
|
|
SYNDROMIC HYPERTROPHIC
CARDIOMYOPATHY |
||
|
Noonan's syndrome |
PTPN11 |
|
|
LEOPARD syndrome |
PTPN11 |
|
|
Friedreich's ataxia |
FRDA |
|
Pathology
Typically,
heart weight is increased and the interventricular septum is hypertrophic,
although virtually any pattern of thickening may occur. In the normal heart, the
true apex is often relatively thinner than other segments. Apical variants
characterized by relative or absolute thickening are rare, although hypertrophy
commonly is predominantly in the distal ventricle below the papillary muscles.
Macroscopically, one often sees a characteristic patch of endocardial
thickening on the septum as a consequence of contact with the anterior leaflet
of the mitral valve, which is correspondingly thickened.
Histologically,
the hallmark of hypertrophic cardiomyopathy is myocyte disarray. This
appearance results from the loss of the normal parallel arrangement of
myocytes, with cells forming in whorls around foci of connective tissue. Marked
variation in the diameter of myocytes and in nuclear size may be noted, as well
as abnormal intercellular connections. Myofibrillar architecture within the
cells is also disorganized. Myocyte and myofibrillar disarray may be seen in
patients with aortic stenosis, long-standing hypertension, and some forms of
congenital heart disease, but the extent and severity in hypertrophic
cardiomyopathy are typically far greater. The distinction may be problematic
from a single myocardial biopsy but rarely is difficult at post mortem, when 5
to 40% of the myocardium may be involved in hypertrophic cardiomyopathy.
Myocytolysis with replacement fibrosis and interstitial fibrosis are also
common, and abnormal small intramural arteries are typically seen within the
fibrotic areas. Patients with extensive fibrosis may have ventricular dilation
and reduced systolic function.
Pathophysiology
Left
ventricular hypertrophy is usually associated with hyperdynamic indices of
systolic performance, impaired diastolic function, and clinical features
suggestive of ischemia. Typically, ejection velocity is increased, and a high
proportion of stroke volume is ejected early in systole. This appearance of
supranormal systolic function is misleading, because indices of systolic
performance taken from the long axis of the left ventricle, rather than the
short axis, often demonstrate impairment of systolic performance.
Diastolic
dysfunction is common, although variable. Many of the characteristic
pathophysiologic features of hypertrophic cardiomyopathy, including abnormal
ventricular geometry, wall thickening, myocyte hypertrophy, myocyte and
myofibrillar disarray, myocardial fibrosis, and ischemia would be expected to
impair diastolic function. In most cases, relaxation is slow and prolonged,
with elevation of diastolic pressures. A few patients have rapid early filling
with restrictive hemodynamic physiology, markedly elevated filling pressures,
and atrial dilation, with evidence of right-sided congestion, which may occur
in the absence of significant myocardial hypertrophy or impairment of systolic
performance. How the recognized genetic mutations cause these histologic and
pathophysiologic changes is poorly understood, but inefficient utilization of adenosine triphosphatase by
the sarcomere may be the final common pathway, because many of the
mitochondrial and metabolic disorders and congenital syndromes that may mimic
hypertrophic cardiomyopathy are associated with changes in adenosine
triphosphatase synthesis and/or regulation.
Clinical Manifestations
The
clinical expression of left ventricular hypertrophy usually occurs during
periods of rapid somatic growth, which may be during the first year of life or
childhood but more typically during adolescence and, occasionally, in the early
20s. The de novo development of myocardial hypertrophy later in life is
uncommon but typically is associated with the development of mild to moderate
systolic hypertension in patients with mutations in myosin-binding protein C.
Most
patients are asymptomatic or have only mild or intermittent symptoms.
Symptomatic progression is usually slow, age related, and associated with a
gradual deterioration in left ventricular function over decades. Fewer than 5%
of patients may have rapid, symptomatic deterioration in association with
progressive myocardial wall thinning, increased left ventricular end-systolic
dimensions, and an overall reduction in systolic performance. Such a rapid
course is not associated with any particular genetic abnormality.
Symptoms and Signs
Symptoms
may develop at any age, even many years after the appearance of
electrocardiographic (ECG) or echocardiographic manifestations of left
ventricular hypertrophy. Occasionally, sudden death may be the initial
presentation. Experience from evaluating families suggests, however, that most
affected individuals have few or only paroxysmal symptoms. Approximately 30% of
adults develop exertional chest pain, which may be atypical, prolonged, and
noted at rest or nocturnally. Postprandial angina associated with mild exertion
is typical. Mild to moderate dyspnea is common in adults and may relate to left
ventricular outflow tract obstruction and/or mitral regurgitation; it probably
develops as a consequence of ventricular diastolic dysfunction and raised
pulmonary venous pressures.
Occasionally,
patients without significant symptoms present with or develop paroxysmal
nocturnal dyspnea. Such episodes suggest transient myocardial ischemia or
arrhythmias, although evaluations often fail to identify the mechanism.
Approximately
20% of patients experience syncope, and a similar proportion complain of
presyncope. Such symptoms are often attributed to arrhythmias, but
documentation may require prolonged ECG monitoring or implantation of an ECG
recorder; in many cases, no underlying cause is identified. Exertion-related
syncope or presyncope raises the suspicion of labile left ventricular outflow
tract obstruction, exertion-related mitral regurgitation, or ischemia.
Palpitations
are a frequent complaint and are usually attributable to supraventricular or
ventricular ectopy or to forceful cardiac contractions. Sustained palpitations
are usually caused by supraventricular tachyarrhythmias. Initial presentation
with a symptomatic arrhythmia, usually atrial fibrillation, is uncommon.
Patients
with distal or apical hypertrophy have fewer symptoms, better exercise
capacity, no arrhythmias, and good prognosis. Occasionally, however, patients
with distal or apical hypertrophy may have severe refractory chest pain or may
present with troublesome supraventricular arrhythmias.
Diagnosis
The initial diagnostic evaluation includes a family
history focusing on premature cardiac disease or death, a comprehensive medical
history focusing on cardiovascular symptoms, a careful physical examination, a
12-lead ECG study, and a two-dimensional echocardiogram. In patients with
resting left ventricular outflow tract obstruction (20%), the physical
examination may demonstrate a rapid upstroke of the arterial pulse, often
followed by a second late systolic peak (spike and dome). The left ventricular
impulse is forceful, and the typical murmur is heard in late systole, loudest
at the left sternal edge, and radiating to the aortic and mitral areas but not
into the neck or axilla. Physiologic and pharmacologic maneuvers that decrease
afterload or venous return (e.g., standing, Valsalva maneuver, inhalation of
amyl nitrite) or contractility (e.g., a post-extrasystole beat) will increase
the intensity of the murmur, whereas interventions that increase afterload and
venous return (e.g., squatting or handgrip) will reduce it (see Table 48-2). In
contrast, in the majority of patients who do not have left ventricular outflow
tract obstruction, the physical signs are subtle and are limited to features
reflecting the hyperdynamic contraction (rapid upstroke pulse) and poorly
compliant right (prominent a wave in jugular venous pressure) and left (S4
gallop, double-apex beat) ventricles.
More
than 90% of patients have abnormal ECG findings, but no changes are disease
specific. The most common abnormalities are left axis deviation (15 to 20%),
abnormal Q waves (25 to 30%, most commonly in inferolateral leads), and ST
segment or T wave changes (>50%). An isolated increase in the QRS voltage
without ST segment changes or T wave inversion is rare in hypertrophic
cardiomyopathy. The presence of predominantly distal or apical thickening is
associated with giant negative T wave inversion on the ECG tracing.
Two-dimensional
echocardiography is the mainstay of diagnostic imaging, although magnetic
resonance imaging and computed tomography provide alternatives if the
echocardiogram is of poor quality. A wall thickness of more than two standard
deviations above the mean, corrected for age, gender, and height, is generally
accepted as diagnostic: in adults, this value is typically
|
|
|
|
FIGURE 2 Hypertrophic
obstructive cardiomyopathy. A, The two-dimensional long-axis parasternal
view shows the chambers of the heart. The left ventricle posterior wall
(LVPW) is thickened, and the most striking abnormality is the hypertrophy of
the interventricular septum (IVS). Another characteristic feature is a
Venturi effect: as blood leaves the left ventricle ( |
|
The echocardiogram
can measure left ventricular outflow tract obstruction, both at rest and after
maneuvers (e.g., amyl nitrite, Valsalva) that may worsen or provoke
obstruction. Patients with
Diagnostic Criteria in Patients and First-Degree Relatives
Because
genetic analysis is not routinely available outside of research centers, the
diagnosis in first-degree relatives relies on the echocardiographic features of
unexplained left ventricular hypertrophy. When genetic testing is available, it
is at best confirmatory in individuals who meet echocardiographic criteria
because the recognized sarcomeric contractile protein gene abnormalities
account for only 60% of the cases of hypertrophic cardiomyopathy. Genetic
testing is most helpful in first-degree relatives who do not meet conventional
echocardiographic criteria but who may, nonetheless, be at risk of the
complications of hypertrophic cardiomyopathy. Given the 50% probability of
disease in a first-degree relative of a patient with hypertrophic
cardiomyopathy, modified diagnostic criteria (Table 4) consider the high
probability that their otherwise unexplained ECG and echocardiographic findings
reflect incomplete disease expression, with the corresponding risks of
complications and of passing the gene to their children.
TABLE 4 -- DIAGNOSTIC CRITERIA FOR HYPERTROPHIC CARDIOMYOPATHY
IN FIRST-DEGREE RELATIVES OF AFFECTED PATIENTS[*]
|
Major Criteria |
Minor Criteria |
|
ECHOCARDIOGRAPHY |
|
|
Left
ventricular wall thickness ≥13 mm in the anterior septum or posterior
wall or ≥15 mm in the posterior septum or free wall |
Left
ventricular wall thickness of |
|
Severe
SAM of the mitral valve (septal-leaflet contact) |
Moderate
SAM of the mitral valve (no mitral leaflet-septal contact) |
|
Redundant mitral valve leaflets |
|
|
ELECTROCARDIOGRAPHY |
|
|
Left
ventricular hypertrophy with repolarization changes (Romhilt and Estes) |
Complete
bundle branch block or (minor) interventricular conduction defects (in left
ventricular leads) |
|
T
wave inversion in leads I and aVL (≥3 mm) (with QRS-T wave axis
difference ≥30 degrees), V3–V6 (≥3 mm) or
II and III and aVF (≥5 mm) |
Minor
repolarization changes in left ventricular leads |
|
Deep
S wave in lead V2 (> |
|
|
Abnormal
Q waves (>40 msec or >25% R wave) in at least two leads from II, III, aVF
(in absence of left anterior hemiblock), and V1–V4; or
I, aVL, V5–V6 |
Unexplained
chest pain, dyspnea, or syncope |
Adapted
from McKenna WJ, Spirito P, Desnos M, et al: Heart 1997;77:130–132.
|
* |
The diagnosis of hypertrophic cardiomyopathy in
first-degree relatives of patients with the disease is based on the presence
of one major criterion or two minor echocardiographic criteria or one minor
echocardiographic and two minor electrocardiographic criteria. aVF =
augmented voltage unipolar left foot lead; aVL = augmented voltage unipolar
left arm lead; SAM = systolic anterior motion. |
When
available, cardiopulmonary exercise testing with metabolic gas exchange
measurements provides an accurate and reproducible assessment of exercise
capacity, which can be followed serially. Cardiac catheterization is rarely
required for diagnosis or management, but it may be indicated when measurement
of intracardiac pressures is required to guide therapeutic decisions (e.g., in
patients with severe mitral regurgitation) and for the exclusion of coexistent
coronary artery disease in patients with chest pain.
Differential Diagnosis
In the presence
of other causes of left ventricular hypertrophy, such as long-standing systemic
hypertension or aortic stenosis, the diagnosis of hypertrophic cardiomyopathy
may be problematic. However, secondary hypertrophy from other causes rarely
exceeds
Treatment
Prognosis
Population
data reveal that the mortality rate in adults is approximately 1% per year from
sudden death, and preliminary data suggest that patients who carry mutations in
cardiac troponin T or in certain β-myosin heavy chain mutations (e.g., Arg403Glu) are at
increased risk of sudden death. The rate of significant embolic events in
individuals followed in tertiary referral centers is 1 to 4% per year. Embolic
strokes are associated with more cardiac symptoms, left atrial enlargement, and
paroxysmal supraventricular arrhythmias.
Enzymatic
Deficiencies
Specific
metabolic enzyme deficiencies also cause increased ventricular mass and
restrictive cardiomyopathy, usually without outflow tract obstruction, through
the accumulation of abnormal metabolites in the myocardium. Fabry's disease
results in intracellular glycolipid accumulation in the myocardium, valves,
vessel walls, skin, cornea, kidneys, gastrointestinal tract, and central
nervous system. Mortality from this X-linked disorder in men results from
multiple organ involvement in the fourth or fifth decade. Heterozygous women
also can develop cardiomyopathy. Glycogen storage disease results from
enzyme deficiencies that lead to excessive deposition of normal glycogen in the
myocardium, skeletal muscle, and liver. The most common is type II, Pompe's
disease, which is associated with dramatic thickening of ventricular septum and
free wall, large QRS amplitude, short PR interval, and death usually within the
first few years of life.
Myocarditis
Definition
Myocarditis, which is an inflammatory process involving cardiac
myocytes, can be caused by infections, immune-mediated damage, or toxins. It
can be defined based on histopathologic or clinical criteria.
Epidemiology
Histologic
diagnostic criteria for myocarditis were met in 1% of more than 12,000
unselected consecutive autopsies in a Swedish study, in up to 20% of unexpected
sudden deaths in young persons, and in 40% of cases of new-onset heart failure
in children. Approximately 5% of a virus-infected population have clinical
evidence of cardiac involvement.
A wide
range of infectious, immune-mediated, toxic, and genetic causes has been
implicated (Table 59-5). Viral genome studies of myocardium obtained by
endomyocardial biopsy reveal evidence of adenovirus, enterovirus, or
cytomegalovirus in 35 to 40% of patients with an acute presentation and
histologic features of myocarditis. Trypanosoma cruzi infection (Chagas'
disease; Chapter 368) is prevalent in South America, hepatitis C (Chapter 152)
myocarditis is more common in
TABLE
59-5 --
CAUSES OF MYOCARDITIS
|
INFECTIONS |
||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||
|
IMMUNE-MEDIATED
DISORDERS |
||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||
|
TOXIC CAUSES |
||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||
|
GENETIC DISORDERS |
||||||||||||||||||||||||||||||||||||||||||
|
Inherited
cardiomyopathies with immune-mediated pathogenesis (dilated and right
ventricular cardiomyopathy) |
Pathobiology
Current
knowledge of viral pathogenesis arises predominantly from inoculation of
enterovirus (often coxsackievirus B3; Chapter 402) into various strains of
mice. Direct myocardial invasion by cardiotropic virus progresses quickly
(<5 to 7 days) to immunologic activation, initially with an inflammatory
cellular infiltration, and later to activation of cell-mediated immunity, as
well as development of autoantibodies directed against contractile
(antimyosin), structural (antisarcolemmal), mitochondrial (adenine nucleotide
translocator), and receptor (anti–β-adrenergic and anti-M2) proteins. In genetically
predisposed mouse strains, immune-mediated myocarditis with production of serum
autoantibodies develops following immunization with the relevant organ-specific
autoantigens (e.g., cardiac myosin) in the absence of viral inoculation,
similar to other autoimmune diseases. In humans, the detection of viral genome following presumed
myocardial infection suggests that viral persistence may contribute to ongoing
myocardial damage as a component of the immunologic response to infection.
Immune-mediated
myocarditis is seen in association with certain systemic inflammatory disorders
but is probably more common when no infectious or associated disorder is
identified. So-called autoimmune myocarditis may reflect progression of
undiagnosed early dilated cardiomyopathy or a response to unrecognized
triggers. Antibiotics, antidepressants, anti-inflammatory agents, and diuretics
may cause hypersensitivity myocarditis that is associated with peripheral
eosinophilia and a myocardial infiltrate with lymphocytes and eosinophils.
Clinical Manifestations
The
clinical presentation is variable, ranging from asymptomatic ECG changes,
symptoms of arrhythmia, or acute coronary syndromes to the new onset of heart
failure. Acute fulminant myocarditis may develop rapidly, with fever,
leukocytosis, severe heart failure, and cardiogenic shock. A viral prodrome is
reported in 10 to 80% of patients who fulfill histologic diagnostic criteria.
Diagnosis
Evaluation
of new-onset features of possible myocarditis should include a history of
cardiac symptoms or premature (<40 years of age) familial cardiac disease. A
careful history and physical examination should be supplemented by both routine
and targeted laboratory testing (Table 59-6). Serum biomarkers of myocardial damage (troponin
I or T) have high (>80%) positive predictive value if performed within 1
month of the onset of symptoms, whereas markers of inflammation appear to have
low sensitivity and specificity. Noninvasive tests including 12-lead and
exercise ECG and two-dimensional echocardiographic studies are recommended.
Other studies of possible value include the following: gallium-67 scintigraphy,
which detects the extent of myocardial inflammation; antimyosin imaging with
indium-111, which detects the extent of myocyte necrosis; and early and late
gadolinium-enhanced magnetic resonance imaging, which reflects both
inflammation and necrosis.
TABLE 6 -- LABORATORY EVALUATION OF CARDIOMYOPATHY
|
CLINICAL
EVALUATION |
|||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||
|
LABORATORY
EVALUATION |
|||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||
|
INITIAL EVALUATION IN SELECTED PATIENTS ONLY |
|||||||||||||||||||||||||||||||||||||||
|
|
* |
Level I recommendations from ACC/AHA 2005 Guideline
Update for the Diagnosis and Management of Chronic Heart Failure in the
Adult. (Hunt SA, Abraham WT, Chin MH, et al: Circulation 2005;112:e154–e235.) |
Histologic
evaluation based on endomyocardial biopsy tissue in patients with new-onset
heart failure does not correlate with symptoms or prognosis, nor does it guide
therapy. In addition, biopsy yields diagnostic information in only 10 to 20% of
patients who present with clinical features of myocarditis. The low yield of
biopsy may relate to sampling error (myocarditis is patchy), the timing of
biopsy (acute versus chronic disease), interobserver variability in
interpretation, and the overall low sensitivity of histologic evaluation in
isolation. Biopsy is generally reserved for patients with heart failure
(subacute or acute) refractory to standard management, features suggestive of
associated cardiac (e.g., conduction defects, arrhythmia) or systemic disease
(e.g., connective tissue disease, amyloidosis, hemochromatosis, sarcoidosis),
or suspicion of giant cell myocarditis because of new-onset heart failure
associated with tachyarrhythmias or conduction disease.
Treatment
|
Treatment
of most patients with myocarditis is supportive. The severity of heart
failure determines the level of pharmacologic intervention and hemodynamic
support. In patients with fulminant myocarditis and severe left ventricular
dysfunction, an aggressive short-term approach (e.g., left ventricular assist
device, extracorporeal membrane oxygenation) is warranted because of the
probability of spontaneous complete recovery. For giant cell myocarditis,
which is a usually fatal disease of relatively young healthy adults, heart
transplantation is the treatment of choice for most patients. Recognition
that pathogenesis involves immune-mediated damage has led to trials of
immunosuppression, but data regarding benefit are unconvincing. In general,
immunosuppression using high-dose prednisolone (tapered over 3 to 6 months
from 60 mg/day down to 5 mg/day) plus azathioprine (1 mg/kg twice daily for ≤6
months) is reserved for patients who have virus-negative myocarditis and
whose disease progresses despite maximal supportive therapy, for patients
with systemic autoimmune disease or progressive sarcoidosis, or for patients
who have idiopathic giant cell myocarditis and are not able to undergo heart
transplantation. |
Prognosis
Patients
with acute myocarditis with mild heart failure or symptoms suggestive of
myocardial ischemia/infarction typically improve within weeks without sequelae.
An acute presentation of myocarditis with advanced heart failure (ejection
fraction <35%) may resolve (25%) but typically (50%) leads to chronic left
ventricular dysfunction (dilated cardiomyopathy) or progresses to death or
cardiac transplantation (25%). Patients who present with acute fulminant
myocarditis, however, have an excellent prognosis, with survival rates of more
than 90%. Giant cell myocarditis is usually fatal without heart
transplantation.
Myocarditis Syndromes
Viral Myocarditis
Viral
myocarditis may be suspected from the clinical picture of recent febrile
illness, often with prominent myalgias, followed by angina-like chest pain,
dyspnea, or arrhythmias. Elevated troponin levels support the diagnosis, and
increasing viral titers (to coxsackievirus, echovirus, adenovirus, or influenza
virus) confirm recent infection. The general prognosis of truly “new-onset”
heart failure attributed to recent viral infection is major improvement in left
ventricular function in up to 50% of patients. If deterioration continues
during the months after diagnosis, the prognosis for recovery becomes poor.
Giant Cell Myocarditis
Patients
with giant cell myocarditis, which accounts for 10 to 20% of biopsy-positive
cases of myocarditis, present with the rapid onset of chest pain, fever, and
hemodynamic compromise, often with ventricular tachycardia and/or
atrioventricular block. When ventricular tachyarrhythmias are a major feature
of myocarditis, particularly in a young person, endomyocardial biopsy is
generally recommended to determine whether giant cell myocarditis is present,
even though the diagnosis is statistically unlikely. Immunosuppression,
although frequently used, does not appear to improve the clinical course, which
is usually characterized by rapid deterioration and death from heart failure
and refractory ventricular tachyarrhythmias unless cardiac transplantation can
be performed.
Human Immunodeficiency Virus
Cardiomyopathy
Clinical
cardiomyopathy occurs in 10 to 40% of patients infected with HIV (Chapter 407),
owing to HIV itself or to coinfection with cytomegalovirus. Treatment is of the
underlying HIV infection.
Chagas' Disease
Chagas'
disease, which is caused by infection with Trypanosoma cruzi, affects up
to 15% of rural populations in South America, is common in
Toxoplasmosis
Toxoplasmosis
myocarditis, owing to intermittent rupture of cysts in the myocardium, can cause
atypical chest pain, arrhythmias, pericarditis, and symptomatic heart failure.
Diagnosis is made from antibody titers. Therapy is with pyrimethamine and
sulfadiazine, but relapses are common.
Lyme Disease
Lyme
carditis classically presents with conduction system abnormalities resulting
from infection with Borrelia burgdorferi, which is diagnosed
serologically. However, isolated cases of heart failure occur.
Immune-Mediated Myocarditis
Myocardial
inflammation can be associated with polymyositis or systemic lupus
erythematosus , although pericarditis and coronary artery vasculitis are more
common. Hypersensitivity reactions, especially to drugs, can cause myocarditis
that often is associated with peripheral eosinophilia and can be confirmed by
endomyocardial biopsy. Treatment includes discontinuation of the offending
agent and corticosteroid therapy.
Peripartum Cardiomyopathy
Peripartum
cardiomyopathy appears in the last month of pregnancy or in the first 5 months
after delivery in the absence of preexisting cardiac disease (Chapter 259). The
incidence is between
Dilated
Cardiomyopathy
Definition and Epidemiology
Dilated
cardiomyopathy is characterized by ventricular dilation and impaired
contractile performance, which may involve the left or both ventricles. It may
develop as a consequence of prior myocarditis or as a result of a recognized
toxin, infection, predisposing cardiovascular disease (e.g., hypertension,
ischemic or valvular heart disease), or systemic metabolic, neuromuscular, or
inflammatory disorder (Table 59-7). For some patients, identification of the
specific cause and associated disease will strongly influence diagnosis,
management, and prognosis, even though the principles related to the management
of heart failure are generic.
TABLE 7 -- CAUSES OF DILATED CARDIOMYOPATHY
|
CARDIOVASCULAR
DISORDERS |
|
Systemic
hypertension |
|
TOXINS |
|
Alcohol |
|
ASSOCIATED SYSTEMIC
DISEASES |
|
Systemic
lupus erythematosus |
|
MUSCULAR DISORDERS |
|
Duchenne's muscular dystrophy |
|
HIGH-OUTPUT STATES |
|
Thiamine deficiency |
In the
population, about 36 persons per 100,000 have unexplained left ventricular
dysfunction with an ejection fraction of less than 40%—a finding that is
indicative of advanced disease. Evidence from population data and family
studies, however, indicates a higher frequency of asymptomatic left ventricular
dysfunction. When no cause or associated disease is identified, dilated
cardiomyopathy has been termed idiopathic, although pedigree studies revealed
that 50 to 60% of such patients have familial disease, and disease-causing
mutations currently can be identified in 10 to 20% of such families.
Pathobiology
In
dilated cardiomyopathy, systolic dysfunction may result from a variety of
causes (e.g., toxins, infection, ischemia) and pathologic states (e.g.,
inflammation, high output, genetic abnormalities). The altered hemodynamic
parameters of decreased stroke volume and increased chamber pressures trigger
the recognized neurohumoral changes of heart failure (Chapter 57) and produce
ventricular remodeling with eccentric hypertrophy and cavity dilation, which is
distinct from the remodeling seen in hypertrophic and restrictive
cardiomyopathy but is similar for all other causes of dilated cardiomyopathy.
The insult to myocyte integrity may be relatively acute and may trigger
programmed cell death (apoptosis); however, insidious progression is the rule
in inherited dilated cardiomyopathy and is also seen with viral persistence,
anthracycline toxicity, and autoimmune dilated cardiomyopathy. The systolic
dysfunction may reflect a combination of irreversible cell death and reversible
dysfunction from inflammatory mediators. Current conventional treatment aims to
minimize myocardial stress and triggers of ongoing inflammatory damage.
Examples of significant improvement in systolic function raise the possibility
of myocardial regenerative capacity, which is being investigated in the context
of stem cell and myoblast therapies.
Dilated
cardiomyopathy that develops in the absence of significant valvular,
hypertensive, or ischemic heart disease is usually familial. Endomyocardial
biopsy and long-term follow-up of asymptomatic relatives suggest a natural
history of slowly progressive, immune-mediated myocardial damage, with
age-related disease expression reaching 90% by the fifth decade. Symptomatic
clinical presentation may be triggered by a respiratory tract infection,
pregnancy, alcohol, or a salt and water load.
The
concept of a trigger with immune-mediated pathogenesis in genetically
predisposed individuals is supported by the finding of mutations in genes
encoding important structural proteins in 20 to 30% of families with dilated
cardiomyopathy; sarcomeric genes (10%) and lamin A/C (5%) are the most common
(Table 59-8). One third of probands and family members develop low-titer,
organ-specific autoantibodies to cardiac α-myosin, antibodies that are rare in other cardiac
diseases or in physiologically normal individuals. The presence of
autoantibodies is associated with markers of early disease and may reflect
exposure of the immune system to the normally unseen intracytoplasmic antigens
from the structurally damaged myocytes. Viral persistence has also been
implicated as an ongoing trigger of immune-mediated damage. Preliminary studies
do not suggest major phenotypic differences among families with mutations that
affect various structural elements in the Z band (i.e., actin), in intermediate
filaments (i.e., actinin), or in binding to the extracellular matrix (i.e.,
dystrophin). Lamin A/C mutations in the nuclear envelope, however, are
associated with several distinct phenotypes, including premature conduction
disease with late-onset dilated cardiomyopathy, severe early dilated
cardiomyopathy with sudden death, and dilated cardiomyopathy in association
with Emery-Dreifuss muscular dystrophy (Chapter 447).
TABLE 8 -- FAMILIAL DILATED CARDIOMYOPATHY: GENES, PROTEINS, AND
PHENOTYPES
|
Gene |
Protein Sarcomeric |
Phenotype |
Comment |
|
MYH7 |
β-Myosin heavy chain |
DCM |
|
|
MYBPC3 |
Cardiac
myosin binding protein C |
DCM |
|
|
TNNT2 |
Cardiac troponin T |
DCM |
|
|
TNNI3 |
Cardiac troponin I |
DCM |
|
|
TPM1 |
α-Tropomyosin |
DCM |
|
|
ACTC |
α-Cardiac actin |
DCM |
|
|
TNNC1 |
Cardiac troponin C |
DCM |
|
|
MYH6 |
α-Myosin heavy chain |
DCM |
Single study |
|
SARCOMERE
AND Z-DISC RELATED |
|||
|
TTN |
Titin |
DCM |
|
|
CRP3 |
Muscle LIM protein |
DCM |
|
|
VCL |
Metavinculin |
DCM |
|
|
LDB3 |
Cypher/ZASP |
DCM, noncompaction |
|
|
INTERMEDIATE FILAMENTS |
|||
|
DES |
Desmin |
DCM |
|
|
LMNA |
Lamin A/C |
DCM,
conduction defect, muscular dystrophy |
|
|
CYTOSKELETAL |
|||
|
DMD |
Dystrophin |
DCM |
X-linked |
|
SGCD |
δ-Sarcoglycan |
DCM |
|
|
ION
CHANNEL AND ION-CHANNEL RELATED |
|||
|
SCN5A |
Cardiac sodium channel |
DCM, conduction defect, arrhythmia |
Single study |
|
SUR2A/ABCC9 |
ATP-sensitive potassium channel |
DCM, rhythm disturbances |
Single study |
|
PLN |
Phospholamban |
DCM |
|
|
MITOCHONDRIAL |
|||
|
G4.5 |
Tafazzin |
DCM, myopathy (Barth's syndrome) |
X-linked |
|
ATP = adenosine triphosphate; DCM = dilated
cardiomyopathy; ZASP = z-band alternatively spliced; PDF = motif protein. |
Clinical Manifestations
The
classic presentation with a gradual decrease in exercise capacity may be
appreciated only in retrospect. The initial presentation is often with acute
decompensation triggered by an unrelated problem, such as anemia,
thyrotoxicosis, or infection. Atypical chest pain may be prominent, perhaps
reflecting myopericarditis. Presentation with an embolic event from the left
ventricle or left atrium or with a sustained arrhythmia is less common.
Symptoms relating to raised filling pressures (e.g., orthopnea, nocturnal
cough, paroxysmal nocturnal dyspnea, peripheral edema) often precede symptoms
of low cardiac output (e.g., dyspnea on exertion). An obvious family history of
dilated cardiomyopathy is present in 5 to 10% of patients, although pedigree
evaluation elicits suggestive evidence of unexplained premature cardiac disease
or embolic events in up to 30% of patients.
Diagnosis
The
diagnosis of dilated cardiomyopathy historically has relied on signs or
symptoms of heart failure accompanied by indices of advanced left ventricular
impairment and dilation. Unexplained less severe abnormalities on physical
examination, 12-lead ECG tracings, or two-dimensional echocardiographic study,
however, may reflect an early stage of disease with the opportunity to
intervene and attenuate or prevent disease progression.
An
early diagnosis of dilated cardiomyopathy requires consideration of the common
recognized causes: systemic hypertension, valvular heart disease, associated
systemic disorders, high-output states, and the muscular dystrophies, each of
which is often suggested by the history, physical examination, 12-lead ECG
study, and two-dimensional echocardiogram. Coronary angiography may be
required, however, to exclude ischemic heart disease in patients with chest
pain, risk factors for coronary disease, or age greater than
40 years. Recommended tests (see Table 59-6) include the following: a complete
blood count; tests of renal, thyroid, and hepatic function; a chest radiograph
to exclude infection; iron and transferrin levels to exclude hemochromatosis;
and creatine kinase levels to exclude subclinical skeletal myopathy. Specific
viral titers may be required if evidence suggests myocarditis (see Table 8).
The ECG
changes of early disease are not specific and may include left axis deviation
and T wave abnormalities. With progressive and advanced disease, conduction
abnormalities develop: PR prolongation, QRS widening, and left bundle branch
block. The rapid development of conduction disease in association with left
ventricular dysfunction may suggest giant cell myocarditis, whereas progressive
conduction disease in the absence of significant left ventricular dysfunction
should raise suspicion of sarcoidosis, myotonic dystrophy (Chapter 447), or
disease caused by a mutation in lamin A/C.
As a
baseline and for serial assessment to monitor disease progression and the
effect of treatment, patients should have a two-dimensional echocardiogram (with
measurement of chamber dimensions and calculated indices of systolic function)
and a maximal exercise test (ideally with metabolic gas exchange measurements)
to provide structural and functional characterization of their disease. Cardiac
magnetic resonance imaging may provide more accurate measurements of
ventricular volume but is generally less practical for serial evaluation.
Gadolinium-enhanced magnetic resonance imaging, however, may be very helpful in
differentiating segmental wall motion abnormalities in dilated cardiomyopathy
from previous myocardial infarction. A myocardial biopsy occasionally should be
considered in patients with potential unexplained myocarditis.
Treatment
|
In
the absence of a specific underlying cause or aggravating factor, treatment
is as described for the various stages of heart failure. Supportive therapy
includes sodium and fluid restriction, avoidance of alcohol and other toxins,
and use of established heart failure medications. Although older
recommendations emphasized rest and avoidance of exercise, this advice should
be limited to patients with myocarditis or peripartum cardiomyopathy; for
other patients, a submaximal exercise regimen is desirable to sustain
mobility, to avoid deconditioning, and to maintain physical and psychological
well-being. Patients with atrial fibrillation or with echocardiographic
evidence of a left atrial or left ventricular mural thrombosis should be
anticoagulated to an international normalized ratio of 2.0 to 3.0. An ICD is
preferred over medication for ventricular arrhythmias, and some patients
require management for advanced heart failure with biventricular pacing,
inotropic medications, ventricular assist devices, and cardiac
transplantation. |
Prevention
Familial
evaluation of first-degree relatives by history, by physical examination, and
with 12-lead ECG and two-dimensional echocardiographic studies is warranted at
the time of diagnosis and serially thereafter. Precise algorithms to determine
the interval of evaluation remain to be determined; in the
absence of acute myocarditis, disease progression is usually slow, and
evaluation about every 5 years until age 50 years appears appropriate. The
detection of early disease in a family member offers an opportunity to initiate
treatment, usually with an angiotensin-converting enzyme inhibitor or β-blocker, but the efficacy of such therapy remains to
be proven.
Prognosis
Prognosis
relates to specific treatable causes (e.g., valvular heart disease) and to the
overall prognosis of any associated disease (e.g., scleroderma). The prognosis
of idiopathic and genetically determined dilated cardiomyopathy is related to
the severity of disease at the time of presentation and the response to initial
treatment. Most patients improve with treatment, but 5-year survival is less
than 50% in patients who present with severe disease (e.g., ejection fraction
<25%, left ventricular end-diastolic dimension >
Specific Causes of Dilated Cardiomyopathy
Alcoholic Cardiomyopathy
In the
Chemotherapy
Doxorubicin
(Adriamycin) cardiotoxicity causes characteristic histologic changes on
endomyocardial biopsy, with overt heart failure in 5 to 10% of patients who
receive doses greater than or equal to 450 mg/m2 of body surface
area. Patients who have received anthracyclines in the prepubertal period
without apparent cardiotoxicity may develop cardiac failure in young adulthood.
The risk is higher in patients who have lower baseline ejection fractions,
concomitant radiation therapy, or higher doses of doxorubicin. Cyclophosphamide
and ifosfamide can cause acute severe heart failure and malignant ventricular
arrhythmias. Imatinib therapy has recently been associated with decreased left
ventricular function. 5-Fluorouracil can cause coronary artery spasm and
depressed left ventricular contractility. Trastuzumab has been associated with
an increased incidence of heart failure, particularly in patients who have
received previous chemotherapy for breast cancer. Interferon-α may be associated with hypotension and arrhythmias in
up to 10% of patients, and interleukin-2 rarely has been associated with
cardiotoxicity. Treatment consists of discontinuation of chemotherapy and,
usually, standard therapy for heart failure.
Metabolic Causes
Excess
catecholamines, as in pheochromocytoma, may injure the heart by
compromising the coronary microcirculation or by direct toxic effects on
myocytes. Cocaine increases synaptic concentrations of catecholamines by
inhibiting reuptake at nerve terminals; the result may be an acute coronary
syndrome or chronic cardiomyopathy.
Thiamine
deficiency from poor nutrition or
alcoholism can cause beriberi heart disease, with vasodilation and high cardiac
output followed by low output. Calcium deficiency resulting from
hypoparathyroidism, gastrointestinal abnormalities, or chelation directly
compromises myocardial contractility. Hypophosphatemia, which may occur
in alcoholism, during recovery from malnutrition, and in hyperalimentation,
also reduces myocardial contractility. Patients with magnesium depletion
owing to impaired absorption or increased renal excretion also may present with
left ventricular dysfunction.
Hypothyroidism depresses contractility and conduction and may cause
pericardial effusions, whereas hyperthyroidism increases cardiac output,
can worsen underlying heart failure, and may rarely be the sole cause of heart
failure. The presenting sign of diabetes can be cardiomyopathy,
especially with diastolic dysfunction, independent of epicardial coronary
atherosclerosis, for which it is a major risk factor. Obesity can cause
cardiomyopathy with increased ventricular mass and decreased contractility,
which improve after weight loss, or it can aggravate underlying heart failure
from other causes.
Skeletal Myopathies
Duchenne's
muscular dystrophy and Becker's X-linked skeletal muscle dystrophy typically
include cardiac dysfunction. Emery-Dreifuss muscular dystrophy with abnormalities
of the anchoring protein emerin occurs in an X-linked pattern, whereas the same
phenotype in an autosomal dominant pattern results from abnormalities of
nuclear laminar proteins. Maternally transmitted mitochondrial myopathies such
as Kearns-Sayre syndrome frequently cause cardiac myopathic changes that can be
rapidly progressive in young adulthood.
Overlap with Restrictive Cardiomyopathy
Diseases
causing primarily restrictive cardiomyopathies (see later) can occasionally
overlap to cause a picture consistent with dilated cardiomyopathy. For example,
hemochromatosis and sarcoidosis should be considered when
evaluating any patient with a cardiomyopathy, although these conditions are
more often considered with the restrictive diseases. Amyloidosis is less
commonly confused with dilated than with hypertrophic cardiomyopathy but should
be considered in a patient with a thick-walled ventricle with moderately
depressed contractile function.
Arrhythmogenic
Right Ventricular Cardiomyopathy
Definition and Epidemiology
Arrhythmogenic
right ventricular cardiomyopathy (Chapter 64) is a genetically determined heart
muscle disorder characterized by fibrofatty replacement of right ventricular
myocardium. It is associated with arrhythmia, heart failure, and premature
sudden death. The disease is seen in patients of European, African, and Asian
descent, with an estimated prevalence in adults of between
Pathobiology
Genetics
Arrhythmogenic
right ventricular cardiomyopathy is inherited as an autosomal dominant disease,
usually with incomplete penetrance, although recessive forms with cutaneous
manifestations are recognized (Table 59-9). To date, recognized mutations
account for approximately 40% of cases. Mutations in the cardiac ryanodine
receptor produce a clinical picture with a closer resemblance to familial
catecholaminergic polymorphic ventricular tachycardia (Chapter 64).
TABLE 9 -- FAMILIAL ARRHYTHMOGENIC RIGHT VENTRICULAR
CARDIOMYOPATHY: GENES, PROTEINS, AND PHENOTYPES
|
Gene |
Protein |
Phenotype |
Comment |
|
DSP |
Desmoplakin |
ARVC
with or without cutaneous abnormalities |
Autosomal dominant or recessive |
|
ARVC,
palmoplantar keratoderma, woolly hair (Carvajal's syndrome) |
Autosomal recessive |
||
|
JUP |
Plakoglobin |
ARVC,
palmoplantar keratoderma, woolly hair ( |
Autosomal recessive |
|
PKP-2 |
Plakophilin-2 |
ARVC |
Autosomal dominant |
|
DSG2 |
Desmoglein-2 |
ARVC |
Autosomal dominant |
|
DSC2 |
Desmoglein-2 |
ARVC |
Autosomal dominant |
|
TGF-β3 |
Transforming growth factor-β3 |
ARVC |
ARVD1 type |
|
RyR2 |
Cardiac ryanodine receptor |
Catecholamine-induced ventricular
tachycardia |
ARVD2 type |
|
ARVC = arrhythmogenic right ventricular
cardiomyopathy; ARVD = arrhythmogenic right ventricular dysplasia. |
Pathology
The
main pathologic feature is progressive loss of right ventricular myocardium,
which is replaced by adipose and fibrous tissue. These changes, which are
localized, begin in the inflow, outflow, and apical regions of the right
ventricle. Aneurysm formation in these areas is typical. Progressive myocardial
involvement may lead to global right ventricular dilation. Severe right
ventricular disease is usually associated with fibrofatty substitution of the
left ventricular myocardium, with the posterolateral wall preferentially
affected.
The
impairment of desmosomal function under conditions of mechanical stress is
hypothesized to cause myocyte detachment and cell death. The acute phase of
myocardial injury may be accompanied by inflammation; repair by fibrofatty
replacement occurs because regeneration in cardiomyocytes is limited. The
increased distensibility of the thin-walled right ventricle appears to confer
vulnerability to cell adhesion defects. Early disease shows predilection for
the thinnest portions of the right ventricle, whereas left ventricular
involvement is often initially in the relatively thin
posterolateral wall with sparing of the thicker septum and free wall.
Clinical Manifestations
In
general, four phases of disease relate to age. In the early phase, patients are
usually asymptomatic, but resuscitated cardiac arrest and sudden death may be
the initial manifestations, particularly in children, adolescents, and young
adults. The overt arrhythmic phase most often first occurs in adolescents and
young adults, when patients note palpitations or syncope. Symptomatic sustained
arrhythmias are usually accompanied by morphologic and functional abnormalities
of the right ventricle. The third phase, characterized by diffuse right
ventricular disease, usually is recognized in the middle and later decades;
patients may present with right-sided heart failure despite relatively
preserved left ventricular function. In the advanced stage, obvious left ventricular
involvement and biventricular heart failure are seen. More than 75% of deaths
occur in patients with prior arrhythmic events and/or clinical heart failure.
Diagnosis
Clinical
evaluation includes inquiry for symptoms of arrhythmia (syncope, presyncope,
sustained palpitation), a family history of premature cardiac symptoms and/or
sudden death, 12-lead, 24-hour, and maximal exercise ECG testing, and
two-dimensional echocardiography with specific right ventricular views.
Contrast echocardiography may be required to obtain better endocardial
definition of the right ventricular myocardium and apex of the left ventricle.
Magnetic resonance imaging may provide accurate assessment of ventricular
volumes as well as noninvasive characterization of fibrous tissue and fat.
Ventricular
arrhythmias with a left bundle branch block morphology, consistent with a right
ventricular origin, are characteristic. Presentation during the arrhythmic
phase may be with an arrhythmia of right ventricular outflow tract origin (left
bundle branch block with inferior axis). However, the ECG and arrhythmic
manifestations are not specific to arrhythmogenic right ventricular
cardiomyopathy and overlap with many other disease states, so standard criteria
are recommended for diagnosis (Table 10). Because these criteria are highly
specific but lack sensitivity for detecting early disease, more sensitive
criteria are recommended for first-degree relatives of known cases (Table 11).
The diagnosis of arrhythmogenic right ventricular cardiomyopathy in a proband
also raises the possibility of mutation analysis throughout the family to
identify those at risk and in need of serial evaluation, as well as those who
need no specific follow-up.
TABLE 10 -- ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY:
CRITERIA FOR DIAGNOSIS IN PROBANDS[*]
|
Major |
Minor |
|
FAMILY HISTORY |
|
|
Familial
disease confirmed at necropsy or surgery |
Family
history of premature sudden death (<35 yr) from suspected ARVC; family
history (clinical diagnosis based on present criteria) |
|
ECG
DEPOLARIZATION/CONDUCTION ABNORMALITIES |
|
|
ϵ
waves or localized prolongation (>110 msec) of QRS complex in right
precordial leads (V1–V3) |
Late
potentials on signal-averaged ECG |
|
ECG REPOLARIZATION
ABNORMALITIES |
|
|
|
Inverted
T waves in right precordial leads (V2 and V3) in
persons >12 years of age and in the absence of right bundle branch block |
|
ARRHYTHMIAS |
|
|
|
Sustained
or nonsustained left bundle branch block–type ventricular tachycardia
documented on ECG or Holter monitoring or during exercise testing; frequent
ventricular extrasystoles (>1000/24 hr on Holter monitoring) |
|
GLOBAL
OR REGIONAL DYSFUNCTION AND STRUCTURAL ALTERATIONS |
|
|
Severe
dilation and reduction of right ventricular ejection fraction with no or mild
left ventricular involvement; localized right ventricular aneurysms (akinetic
or dyskinetic areas with diastolic bulgings); severe segmental dilation of right
ventricle |
Mild
global right ventricular dilation or ejection fraction reduction with normal
left ventricle; mild segmental dilation of right ventricle; regional right
ventricular hypokinesia |
|
TISSUE CHARACTERISTICS
OF WALLS |
|
|
Fibrofatty
replacement of myocardium on endomyocardial biopsy |
|
From
McKenna WJ, Thiene G, Nava A, et al: Diagnosis of arrhythmogenic right
ventricular dysplasia/cardiomyopathy. Br Heart J
1994;71:215–218.
|
* |
Diagnosis requires two major, one major and two
minor, or four minor criteria. ARVC
= arrhythmogenic right ventricular cardiomyopathy; ECG = electrocardiogram. |
TABLE 11 -- ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY:
CRITERIA FOR DIAGNOSIS OF FIRST-DEGREE RELATIVES WHO DO NOT FULFILL CRITERIA AS
PROBANDS[*]
|
ARVC
in a first-degree relative plus one of the following: |
|
|
ECG |
T
wave inversion in right precordial leads (V2 and V3) |
|
Signal-averaged ECG |
Late
potentials seen on signal-averaged ECG |
|
Arrhythmia |
Left
bundle branch block–type ventricular tachycardia on ECG, Holter monitoring,
or during exercise testing; >200 extrasystoles over a 24-hour period |
|
Structural
or functional abnormality of the right ventricle |
Mild
global right ventricular dilation or reduction in ejection fraction with
normal left ventricle; mild segmental dilation of the right ventricle;
regional right ventricular hypokinesia |
From
Hamid MS, Norman M, Quraishi A, et al: Prospective evaluation of relatives for
familial arrhythmogenic right ventricular cardiomyopathy reveals a need to
broaden diagnostic criteria. J Am Coll Cardiol 2002;40:1445–1450.
|
ARVC = arrhythmogenic right ventricular
cardiomyopathy; ECG = electrocardiogram. |
|
* |
Any one criterion is adequate for the diagnosis. |
Differential Diagnosis
The
differential diagnosis includes other inherited cardiomyopathies (e.g.,
hypertrophic, dilated), the inherited arrhythmias (long QT syndrome, Brugada
syndrome, and catecholaminergic polymorphic ventricular tachycardia; Chapter
64) as well as anomalous coronary arteries (Chapter 56). The differentiation
from so-called benign right ventricular outflow tract tachycardia may be
problematic, although in the latter the 12-lead ECG and right ventricular
imaging studies are typically normal, and no familial disease is present.
Treatment
|
Treatment
of patients with symptomatic ventricular arrhythmias is with an ICD, with
supplemental metoprolol (50 to 200 mg/day), sotalol (160 to 240 mg/day), or
even amiodarone (maintenance dose of 200 mg/day) if needed because of atrial
fibrillation or frequent shocks. |
Restrictive
Cardiomyopathy
Definition and Epidemiology
Restrictive
cardiomyopathies are characterized by impaired filling and reduced diastolic
volume of the left and/or right ventricle despite normal or near-normal
systolic function and wall thickness. Primary forms are uncommon, whereas
secondary forms, in which the heart is affected as part of a multisystem
disorder, usually present at the advanced stage of an infiltrative disease
(e.g., amyloidosis or sarcoidosis) or a systemic storage disease (e.g.,
hemochromatosis). Idiopathic restrictive cardiomyopathy affects both male and
female patients and may manifest in children and young adults.
Pathobiology
Genetics
Restrictive
cardiomyopathy may be familial. Of the secondary forms, transthyretin
amyloidosis (Chapter 296), hemochromatosis, several of the glycogen storage
diseases (Chapter 219), and Fabry's disease (Chapter 223) all have a genetic
basis (Table 59-12). Familial idiopathic restrictive cardiomyopathy also is
part of the genetic and phenotypic expression of hypertrophic cardiomyopathy
caused by sarcomeric contractile protein gene abnormalities. Restrictive
cardiomyopathy has also been reported in association with skeletal myopathy and
conduction system disease as part of the phenotypic spectrum caused by
mutations in lamin A or C.
TABLE 12 -- CAUSES OF RESTRICTIVE CARDIOMYOPATHIES
|
INFILTRATIVE DISORDERS |
|
Amyloidosis |
|
STORAGE DISORDERS |
|
Hemochromatosis
|
|
FIBROTIC DISORDERS |
|
Radiation |
|
METABOLIC DISORDERS |
|
Carnitine
deficiency |
|
ENDOMYOCARDIAL
DISORDERS |
|
Endomyocardial
fibrosis |
|
MISCELLANEOUS CAUSES |
|
Carcinoid syndrome |
Pathophysiology
The
characteristic dip and plateau (or square root) hemodynamic pattern (Fig. 59-4)
during diastole, which is caused by an increased stiffness of the endocardium
or myocardium, induces ventricular pressures to rise disproportionately to
small changes in volume until a maximum is reached. In infiltrative
diseases such as amyloidosis or sarcoidosis, the increased stiffness results
from infiltrates within the interstitium between myocardial cells. In the
storage disorders, the deposits are within the cells.
|
|
|
|
FIGURE 4 Idiopathic restrictive cardiomyopathy.
Right ventricular (RV) and left ventricular ( |
|
Clinical Manifestations
The
presenting clinical features develop as a consequence of raised ventricular
filling pressures and are generally not distinguishable from those of heart
failure resulting from systolic impairment. In the early stages, the patient
may have a decrease in exercise capacity, whereas advanced disease is typically
associated with extreme fatigue and dyspnea at rest as part of a low cardiac
output state. Atrial dilation and atrial fibrillation are common. Pulmonary
congestion, hepatic engorgement, ascites, and peripheral edema develop with
advanced disease.
Diagnosis
Diagnosis
is based on the demonstration of the abnormal filling pattern and can most
usefully be achieved by Doppler echocardiographic evaluation. Contrast
echocardiography or magnetic resonance imaging is useful to delineate the
distribution of disease and the extent of mitral and tricuspid valve
involvement.
The
diagnostic evaluation aims to exclude potentially reversible conditions (e.g.,
most of the secondary causes of restrictive cardiomyopathy). In such cases, the
cardiac manifestations may provide the clues, but definitive diagnosis relies
on the demonstration of disease-specific features, such as the following: the
presence of abnormal amyloid protein in amyloidosis, a noncaseating granuloma
in sarcoidosis (Chapter 95), abnormal iron studies in hemochromatosis, and reduced α1-galactosidase
levels in Fabry's disease. Endomyocardial biopsy, although potentially
definitive, is rarely required to make these diagnoses. It is often important
to exclude constrictive pericarditis, which is also characterized by rapid
early diastolic filling.
Differential Diagnosis
In
pericardial constriction, the capacity of the heart to expand is limited by the
rigid pericardium, so increases in filling pressures will not result in an
increased cardiac volume. In restrictive cardiomyopathy, by comparison,
increases in volume will increase filling pressures and, as a result, increase
systemic blood pressure; by the same principle, patients with restrictive
cardiomyopathy may be very sensitive to volume depletion.
Although
the strictest definition of a restrictive cardiomyopathy requires normal or
near-normal left ventricular systolic function and wall thickness with the dip
and plateau hemodynamic pattern, diastolic impairment with or without
restrictive physiology is also part of the spectrum of the clinical
presentation of both hypertrophic and dilated cardiomyopathies. Patients with
hypertension also may first present with diastolic dysfunction and mild left
ventricular hypertrophy before progressing to more marked left ventricular
hypertrophy or dilation.
Treatment
|
In patients with secondary restrictive
cardiomyopathies, treatment must address both the underlying systemic disease
and the heart failure itself (Tables 2 through 5). Diuresis is key but must
be undertaken carefully so as not to reduce left ventricular filling
pressures to the point of causing hypotension. Angiotensin-converting enzyme
inhibitors and β-blockers are commonly recommended despite fewer
data on their benefit than in dilated cardiomyopathy. For idiopathic
restrictive cardiomyopathy, treatment of heart failure is the only option. |
Prognosis
In
restrictive cardiomyopathy, the clinical course is usually slow and protracted
with an antecedent history that, in retrospect, may go back 5 years or more.
Survival from the time of diagnosis is often 10 years or more, except for
amyloidosis, which progresses much more rapidly. Symptoms of heart failure with
mitral and tricuspid regurgitation are generally progressive and respond poorly
to treatments for heart failure. Referral for transplant assessment should be
considered early because pulmonary hypertension may develop and necessitate
heart and lung transplantation.
Specific Clinical Syndromes
Sarcoidosis
Although
cardiac involvement is found in up to 50% of patients with sarcoidosis (Chapter
95) at autopsy, clinical cardiac involvement occurs in fewer than 10% of
patients. The presentation is often with conduction defects or ventricular
tachyarrhythmias, although granulomas can also compromise the coronary
circulation and cause ischemia or infarction. On echocardiogram, the
cardiomyopathy may be dilated or restrictive. Biopsy of extracardiac sites is
usually adequate for the diagnosis, but a gallium scan often demonstrates
cardiac inflammation. A myocardial biopsy may show granulomas or, because of
the focal distribution of the lesions, may be nondiagnostic. Corticosteroid
therapy may improve arrhythmias, but heart failure may worsen despite such
therapy. An ICD is generally indicated for ventricular arrhythmias.
Amyloidosis
Amyloidosis,
which is the most common cause of restrictive cardiomyopathy, can result from
either primary amyloidosis in patients with multiple myeloma or familial
amyloidosis in patients in whom an abnormal transthyretin is deposited in the
kidney, liver, and sometimes the heart. By comparison, secondary amyloidosis
rarely involves the heart. Senile amyloidosis, involving normal transthyretin,
occasionally causes clinical heart failure in elderly patients but progresses
quite slowly compared with primary amyloidosis. Amyloid fibrils infiltrate into
the interstitium, stiffen the ventricles, replace some contractile elements,
and frequently affect the conduction system, thereby leading to
bradyarrhythmias. When amyloid also surrounds the arterioles, it may lead to
anginal chest pain and even myocardial infarction. Some patients may present
with orthostatic hypotension resulting from amyloid autonomic neuropathy.
Macroglossia, carpal tunnel syndrome with hypothenar wasting, skin friability,
nephrotic syndrome, or multiple myeloma may also suggest the diagnosis of
amyloidosis.
The ECG
tracing characteristically shows markedly decreased voltage despite increased
wall thickness on echocardiography. Specific diagnosis in some cases can be
made from a characteristic sparkling refractile pattern on echocardiography
(Fig. 5). Up to 80% of patients have a monoclonal protein identified from
either serum or urine. Biopsy of subcutaneous fat or the rectum frequently
reveals amyloidosis, so endomyocardial biopsy is rarely required.
|
|
|
|
FIGURE 5 Amyloidosis. A, Parasternal
long-axis echocardiographic image shows a “sparkling” granular myocardial
texture in the interventricular septum in a patient with biopsy-proved
amyloidosis. LA = left atrium; |
|
Therapy
with colchicine or with combined melphalan and prednisone provides a 20 to 30%
response rate in patients with monoclonal gammopathy. Vasodilator therapy is
less effective than in dilated cardiomyopathy, owing to less pronounced
systolic dysfunction, greater reliance on high filling pressures, and the
frequently accompanying autonomic neuropathy, which predisposes to postural
hypotension. Amyloidosis is usually a contraindication to cardiac
transplantation because it recurs in the donor heart and can progress rapidly
in other organs.
Patients
with amyloidosis with heart failure have a median survival of less than 1 year
and a 5-year survival of less than 5%. Most deaths occur suddenly. Patients
with familial amyloidosis have a slower course than do patients with a
monoclonal gammopathy.
Hemochromatosis
In
hemochromatosis , which can result from a genetic defect in iron regulation or
from iron overload related to hemolytic anemia and transfusions, iron in the
perinuclear areas of myocytes disrupts cellular architecture and mitochondrial
function, thereby leading to cell death and replacement fibrosis. The
atrioventricular node may be involved. Restrictive physiologic features
dominate earlier in the course, followed by dilation generally to a left
ventricular diastolic dimension less than
Fabry's Disease
In
Fabry's disease and glycogen storage diseases, restrictive physiology is
associated with increases in left ventricular mass (see Hypertrophic
Cardiomyopathy). Treatment is for the underlying systemic disease, with careful
treatment of the heart failure caused by the restrictive myopathy.
Fibrotic Restrictive Cardiomyopathies
Radiation
therapy for thoracic malignant disease can produce restrictive cardiomyopathy,
usually within several years, although occasionally up to 15 years later, and
sometimes with constrictive pericarditis. In the scleroderma-affected heart,
interstitial fibrosis is common, perhaps related to small vessel ischemia with
microinfarction; left ventricular dilation is uncommon, and the congestive
symptoms may be refractory to therapy.
Unclassified
Cardiomyopathies
Left Ventricular Noncompaction
Failure
of the trabecular or spongiform layer of the myocardium to compact may occur
with congenital heart disease, including atrial and ventricular septal defects
and coarctation of the aorta (Chapter 68), and with the rare X-linked
multisystem disorder, Barth's syndrome. With recent improvements in imaging
technology, it has also been recognized in patients with hypertrophic and
dilated cardiomyopathy. The prevalence of localized areas of noncompaction is
unknown, but clinically significant, isolated left ventricular noncompaction in
the absence of other cardiac abnormalities is uncommon.
Areas
of noncompacted myocardium may be best delineated from normal myocardium by the
demonstration of flow within the myocardium by Doppler or contrast
echocardiography. When extensive areas are involved, systolic performance may
be impaired, and there is a risk of ventricular arrhythmias and systemic
emboli. Treatment, when necessary, is for associated heart failure,
arrhythmias, and the risk of emboli. Natural history and
prognosis are not well established.
Tako-Tsubo
cardiomyopathy is a syndrome of transient apical left ventricular dysfunction
that mimics myocardial infarction. Postulated mechanisms include coronary
artery spasm, myocarditis, and dynamic midcavity obstruction. Analogous
permanent apical outpouchings develop in patients with hypertrophic
cardiomyopathy and midventricular obstruction.
The
clinical syndrome classically includes chest pain, ST segment elevation, and
raised cardiac biomarkers in association with emotional or physical stress.
Coronary arteriography reveals normal epicardial vessels. Conservative
treatment with rehydration and removal of the determinants of stress usually
results in rapid resolution within hours of the symptoms, ECG changes, and wall
motion abnormalities.
PERICARDIAL DISEASE
The
pericardium is composed of two distinct layers. The fibrous parietal
pericardium provides a protective sac around the heart to prevent sudden
cardiac dilation and to minimize bulk cardiac motion. The inner, visceral
pericardium is intimately related to the surface of the heart. These two layers
are normally separated by 10 to 50 mL of clear fluid, an ultrafiltrate of
plasma that is produced by the visceral pericardium and functions as a
lubricant to minimize frictional forces between the heart and the pericardium.
In health, the intrapericardial pressure is slightly negative.
Although
congenital total absence of the pericardium is not associated with clinical
disease, partial or localized absence of pericardium, specifically around the
left atrium, may be associated with focal herniation and subsequent
strangulation. This condition, usually diagnosed by thoracic computed
tomography (CT) or magnetic resonance imaging (MRI), has been associated with
atypical chest pain or sudden death; surgical repair often is recommended when
a partial pericardial defect is confirmed. Benign pericardial cysts are rare
and often seen as rounded or lobulated structures adjacent to the usual cardiac
silhouette on the chest radiograph or adjacent to the right atrium on
transthoracic echocardiography.
Acquired
pericardial disease may have numerous causes, most of which produce responses
that are pathophysiologically and clinically similar. These responses most
frequently result in acute pericarditis, pericardial effusion, or constrictive
pericarditis.
|
|
|
|
FIGURE 1 A, Transverse
(axial) magnetic resonance image. Note the
anterior pericardial cyst (straight white arrows) and the normal pericardium
(curved white arrow). B, Transthoracic echocardiogram from the apical
four-chamber view demonstrating a pericardial cyst (Cy) anterior to the right
atrium (RA). The left atrium (LA) and descending thoracic aorta (DO) are also
seen in this view. |
|
Definition
The
most common clinical pathologic process involving the pericardium is acute
pericarditis. Although multiple causes are possible (Table 1), the most common
are viral infection and unknown (idiopathic). Classically, this disorder is
characterized by chest pain, pericardial friction rub, diffuse
electrocardiographic changes, and pericardial effusion, although sometimes
neither electrocardiographic changes nor a pericardial effusion is present. The
clinical syndrome is often relatively brief (days to weeks) in duration and
uncomplicated, although vigilance for progression to tamponade is always
prudent.
TABLE
1
--
ETIOLOGY OF PERICARDITIS
|
INFECTIOUS PERICARDITIS |
|||||||||||||||||||||||||||||||||||||||||||||
|
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|
NONINFECTIOUS PERICARDITIS |
|||||||||||||||||||||||||||||||||||||||||||||
|
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|
HYPERSENSITIVITY
PERICARDITIS |
|||||||||||||||||||||||||||||||||||||||||||||
|
Clinical
Manifestations
Chest
pain of acute infectious (viral) pericarditis typically develops in young
adults (18 to 30 years) 1 to 2 weeks after a “viral illness.” The symptoms are sudden
and severe in onset, characteristically with retrosternal or left precordial
pain and referral to the back and trapezius ridge. Pain may be preceded
by low-grade fever (in contrast to myocardial infarction, in which the pain
precedes the fever). Although radiation to the arms in a manner similar to
myocardial ischemia also may occur, it is less common. The pain is often
pleuritic (e.g., accentuated by inspiration or coughing) and may be aggravated
(supine or left lateral decubitus posture) or relieved (upright posture) by
changes in posture.
The
physical examination in patients with acute pericarditis is most notable for a
pericardial friction rub. Although classically described as triphasic, with systolic and early
(passive ventricular filling) and late (atrial systole) diastolic components,
more commonly a biphasic (systole and diastole) or a monophasic rub may be
heard. The rub may be transient and positional, often best appreciated in the
supine or left lateral decubitus posture. Low-grade fever, resting tachycardia,
and atrial ectopy are common, but atrial fibrillation is unusual.
Diagnosis
Diagnosis
must proceed expeditiously to exclude emergent problems (Fig. 2).
Electrocardiographic changes (Fig. 3) are common, particularly with an infectious
etiology because of associated inflammation of the superficial epicardium.
During the initial few days, diffuse (limb leads and precordial leads) ST
segment elevations occur in the absence of reciprocal ST segment depression. PR
segment depression also is common and reflects atrial involvement. After
several days, the ST segments normalize and then the T waves become inverted
(in contrast to the electrocardiographic changes seen with myocardial
infarction, in which the temporal relationship of the T wave inversions is
earlier and precedes normalization of the ST segment changes). In a large
pericardial effusion, tachycardia, loss of R wave voltage (absolute R wave
magnitude of
|
|
|
|
FIGURE 2 Initial
management of patients with pericarditis. ASA, aspirin;
CXR, chest radiograph; ECG, electrocardiogram; JVP, jugular venous pressure;
NSAIDs, nonsteroidal anti-inflammatory drugs. |
|
|
|
|
|
FIGURE 3 A 12-lead
electrocardiogram from a patient with acute pericarditis. Note the diffuse
ST-T wave changes and PR elevation in lead aVR and PR segment depression in
leads II and aVF and in the precordial leads. |
|
|
|
|
|
FIGURE 4 Lead II rhythm
strip taken from a patient with acute pericarditis complicated by a large
pericardial effusion and tamponade physiology. Note the resting
sinus tachycardia with relatively low voltage and electrical alternans. |
|
If the
pericardial effusion is minimal, the chest radiograph is often unrevealing,
although a small left pleural effusion may be seen. With larger effusions (see
below Pericardial Effusion), there may be a loss of distinct cardiac contours
and “water bottle” appearance to the cardiac silhouette (Fig. 5).
|
|
|
|
FIGURE 5 Posteroanterior
chest radiograph in a patient with a large pericardial effusion. Note the loss of
customary heart borders and a “water bottle” configuration. |
|
|
In the absence of significant pericardial effusion
(see later), treatment that is directed primarily at relieving the patient's
symptoms can be successful in 85% or so of cases on an outpatient basis.
Among nonsteroidal anti-inflammatory drugs, indomethacin (25 to 50 mg three
times daily) is commonly prescribed, but ibuprofen (300 to 800 mg three or
four times a day) or aspirin (325 to 650 mg three times daily) also may be
used. Glucocorticoids (prednisone, 20 to 60 mg/day) may be useful for
resistant situations. Anti-inflammatory drugs should be continued at a
constant high dose until the patient is afebrile and asymptomatic for 5 to 7
days, followed by a gradual taper during the next several weeks. The use of
warfarin or heparin should be avoided to minimize the risk of
hemopericardium, but anticoagulation may be required in atrial fibrillation
or in the presence of a coexistent prosthetic valve. Avoidance of vigorous
physical activity is recommended during the acute and early convalescent
periods. For patients with a first episode of viral or idiopathic
pericarditis, colchicine (0.6 to 1.2 mg/day for 3 to 12 months) reduces the
recurrence rate from about 32% to about 11%. Colchicine is also
effective in patients with familial Mediterranean fever. Viral
and idiopathic pericarditis usually is self-limited, but a quarter of
patients may have recurrent pericarditis. For this group, prolonged treatment
with nonsteroidal anti-inflammatory drugs (e.g., ibuprofen, 300 to 600 mg
three times a day) plus colchicine (0.6 mg twice daily, declining to once
daily after a year) should be considered.[2] For the 10 to 14% of
patients who are intolerant of colchicine and have recurrent episodes despite
high-dose nonsteroidal anti-inflammatory drugs (e.g., indomethacin, 50 mg three
times a day, or ibuprofen, 800 mg four times a day), oral steroids (e.g.,
prednisone, 60 mg with a 2- to 4-week taper) and pericardiectomy should be
considered. Patients with recurrent pericarditis are at increased risk for
progression to constrictive pericarditis. |
PERICARDIAL EFFUSION
Excess
fluid may develop in the pericardial space in all forms of pericardial disease
(Table 2). Most commonly, the fluid is exudative and reflects pericardial
injury or inflammation. Serosanguineous effusions are typical of tuberculous
and neoplastic disease but also may be seen in uremic and viral or idiopathic
disease or in response to mediastinal irradiation. Hemopericardium is seen most
commonly with trauma, myocardial rupture after myocardial infarction,
catheter-induced myocardial or epicardial coronary artery rupture, aortic
dissection with rupture into the pericardial space, or primary hemorrhage in
patients receiving anticoagulant therapy (often after cardiac valve surgery).
Chylopericardium is rare and results from leakage or injury to the thoracic
duct.
TABLE 2 -- PRESENTATION AND TREATMENT OF THE MOST
COMMON SPECIFIC CAUSES OF PERICARDITIS
|
Type of Cause |
Pathogenesis or
Etiology |
Diagnosis |
Treatment |
Complications |
Comments |
||||||||||||||||||||||||||||||
|
Viral |
|
|
Symptomatic relief, NSAIDs |
|
Peaks
in spring and fall |
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|
Tuberculosis |
Mycobacterium
tuberculosis |
|
|
|
1–8%
of patients with tuberculosis pneumonia; rule out HIV infection |
||||||||||||||||||||||||||||||
|
Bacterial |
|
|
|
Tamponade
in one third of patients |
Very
high mortality rate if not recognized early |
||||||||||||||||||||||||||||||
|
Post myocardial infarction |
12 hours–10 days after infarction |
|
|
Tamponade rare |
|
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|
Uremic |
|
Pericardial rub: 90% |
|
|
|
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|
Neoplastic |
In
order of frequency: lung cancer, breast cancer, leukemia and lymphoma, others |
|
|
|
|
Modified
from Malik F, Foster E: Pericardial disease. In
Wachter RM, Goldman L, Hollander H (eds): Hospital Medicine, 2nd ed. Philadelphia,
Lippincott Williams & Wilkins, 2005, p 449.
|
CT = computed tomography; HIV = human immunodeficiency
virus; MRI = magnetic resonance
imaging; NSAIDs = nonsteroidal anti-inflammatory drugs. |
Although the presence of pericardial effusion
indicates underlying pericardial disease, the clinical relevance of the
pericardial effusion is associated most closely with the rate of fluid
collection, intrapericardial pressure, and subsequent development of tamponade
physiology. A rapidly accumulating effusion, as in hemopericardium caused by
trauma or aortic dissection, may result in tamponade physiology with collection
of only 100 to 200 mL. By comparison, a more slowly developing effusion
(hypothyroidism or chronic renal failure) may allow gradual stretching of the
pericardium, with effusions exceeding 1500 mL in the absence of hemodynamic
embarrassment.
Diagnosis
Pericardial
effusion often is suspected clinically when the patient has symptoms and signs
of tamponade physiology (see later), but it also may be suggested first by
unsuspected cardiomegaly on the chest radiograph, especially if loss of the
customary cardiac borders and a water bottle configuration are noted (Fig. 5).
Fluoroscopy, which may display minimal or absent motion of cardiac borders, is
performed commonly when myocardial or epicardial coronary artery perforation is
suspected during a diagnostic or interventional percutaneous procedure.
In most
situations, two-dimensional transthoracic (surface) echocardiography is the
diagnostic imaging procedure of choice for the evaluation and qualitative
assessment of suspected pericardial effusion (Fig. 6). In emergency situations,
it can be performed at the bedside. The subcostal four-chamber view is the most
informative imaging plane; it is particularly relevant because it allows the
size and location of the effusion to be assessed from an orientation that determines
whether the effusion can be drained percutaneously. Transudative effusions
typically appear relatively echolucent (see Fig. 6), whereas
organized-exudative and hemorrhagic effusions have an echo-filled or a
ground-glass appearance (Fig. 7). Stranding, which may be appreciated in
organized or chronic effusions, suggests loculation and an inability to drain
the effusion fully by
percutaneous approaches. In patients with large effusions, which are associated
with electrical alternans (see Fig. 4), the heart may appear to swing freely
within the pericardial sac.
|
|
|
|
FIGURE 6 Transthoracic
echocardiogram from the subcostal approach.
Note the large echolucent area/pericardial effusion (arrows) surrounding the
heart. The right ventricle is compressed. |
|
|
|
|
|
FIGURE 7 Transthoracic
echocardiogram from the parasternal long-axis window in a different patient
than the one in Figure 77-6. Note the large echo-filled pericardial effusion
posterior (straight white arrows) to the left ventricle and anterior (curved
white arrow) to the right ventricle. This patient had a hemorrhagic
pericardial effusion that developed several weeks after aortic valve
replacement and long-term warfarin treatment. A pleural effusion (black
arrow) also is seen. |
|
Cardiac Tamponade
Accumulation
of fluid in the pericardium with a resultant increase in pericardial pressure
and impairment of ventricular filling results in cardiac tamponade. Although
progression to tamponade, which may be fatal if it is not recognized quickly
and treated aggressively, occurs in 10 to 15% of patients with idiopathic
pericarditis, it develops in more than 50% of patients with oncologic,
tuberculous, or purulent pericarditis. The hallmarks of cardiac tamponade are
increased intracardiac pressure and the resulting impaired ventricular filling
and depressed cardiac output. In tamponade, ventricular filling is impaired
throughout diastole; by comparison, early diastolic filling is relatively
normal with pericardial constriction. Invasive hemodynamic assessment reveals
equalization of right and left atrial and right and left ventricular diastolic
pressures. Tamponade may not be an “all-or-none” phenomenon; mild or
“low-pressure” tamponade can be seen when intrapericardial pressures are only
modestly elevated, with resultant equalization of atrial pressures but not
diastolic ventricular pressures.
Clinical Manifestations
The
clinical features of cardiac tamponade may mimic those of heart failure, with
dyspnea on exertion, orthopnea, and hepatic engorgement. Many clinical features
help distinguish cardiac tamponade from constrictive pericarditis and
restrictive cardiomyopathy (Table 3). The typical physical examination with
tamponade includes jugular venous distention with a prominent x descent
(Fig. 8), sinus tachycardia with hypotension, narrow pulse pressure, elevated
(>
TABLE 3 -- COMPARISON OF PHYSICAL EXAMINATION
FINDINGS AND DIAGNOSTIC TEST RESULTS FOR CARDIAC TAMPONADE, CONSTRICTIVE
PERICARDITIS, AND RESTRICTIVE CARDIOMYOPATHY
|
Characteristic |
Cardiac
Tamponade |
Constrictive
Pericarditis |
Restrictive
Cardiomyopathy |
|
CLINICAL |
|||
|
Pulsus paradoxus |
+ |
+/− |
− |
|
Prominent y descent |
− |
+ |
− |
|
Prominent x descent |
+ |
+ |
− |
|
Kussmaul's sign |
− |
+ |
− |
|
S3 or pericardial “knock” |
− |
+ |
+ |
|
S4 |
− |
− |
+ |
|
ELECTROCARDIOGRAPHY |
|||
|
Low voltage |
+ |
+ |
+ |
|
Abnormal P waves |
− |
+ |
+/− |
|
Electrical alternans |
+ |
− |
+ |
|
CHEST RADIOGRAPHY |
|||
|
Cardiomegaly |
+ |
− |
− |
|
Pericardial calcification |
− |
+ |
− |
|
ECHOCARDIOGRAPHY |
|||
|
Pericardial effusion |
+ |
− |
− |
|
Pericardial thickening |
− |
+ |
− |
|
Small right ventricle |
+ |
− |
− |
|
Thickened myocardium |
− |
− |
+ |
|
Enhanced
respiratory variation in E wave |
+ |
+ |
− |
|
COMPUTED
TOMOGRAPHY, MAGNETIC RESONANCE IMAGING |
|||
|
Pericardial thickening |
− |
+ |
− |
|
Pericardial calcification |
− |
+ |
− |
|
CARDIAC CATHETERIZATION |
|
|
|
|
Equalization of pressures |
+ |
+ |
− |
|
Abnormal myocardial biopsy |
− |
− |
+ |
|
|
|
|
FIGURE 8 Simultaneous
right atrial (RA), intrapericardial, and femoral artery (FA) pressure
recordings in a patient with cardiac tamponade.
Note the elevated and equilibrated intrapericardial and right atrial
pressures with a prominent x descent and blunted y descent suggestive
of impaired right atrial emptying in early diastole. The arterial pulse
pressure is narrowed. |
|
Diagnosis
For
patients in whom the history or physical examination suggests tamponade,
emergency transthoracic echocardiography is imperative and generally
diagnostic. Echocardiographic evidence of tamponade physiology includes a
compressed or small right ventricular chamber with late diastolic invagination
of the right atrial and right ventricular free wall on two-dimensional imaging
(Chapter 53). Because of the frequent coexistence of tachycardia, diastolic
invagination sometimes is appreciated best with higher temporal resolution
M-mode echocardiography. In addition to diastolic invagination, M-mode
echocardiography also may show exaggerated inspiratory septal motion and
variation in the duration of aortic valve opening. Localized right atrial, left
atrial, and left ventricular diastolic collapse also may be seen and is
particularly relevant for loculated effusions, such as effusions after trauma
and cardiac surgery. Pseudoprolapse of the mitral valve may be seen because of
the compressed left ventricular cavity. When surface echocardiography is
inadequate, as in a post-thoracotomy patient or a patient with chest wall
trauma, transesophageal echocardiography may be helpful.
Treatment
|
When
tamponade is suggested clinically and confirmed on echocardiography, acute
management includes maintenance of systolic blood pressure with volume
resuscitation. In dire circumstances, immediate pericardiocentesis may be
life-saving (Fig. 77-9). When time allows, right-sided heart catheterization
should be performed to confirm elevated intrapericardial pressure and
“equalization” of right atrial, left atrial, pulmonary capillary wedge, right
ventricular diastolic, and left ventricular diastolic pressures. If echocardiography
shows at least Hemodynamically
significant effusions of less than
|
Approach to Effusion without Tamponade
For
patients with suspected pericardial effusion, transthoracic echocardiography is
the initial test of choice and in most patients is definitive in confirming the
presence or absence of a significant pericardial effusion (loculated effusions
may be identified better by CT or MRI). If a small (0.5 to
In a
moderate (1 to
Chronic or Recurrent Pericardial Effusions
With
chronic or recurrent pericarditis from any cause, pericardial calcification
develops and can be appreciated by thoracic CT (Fig. 10). Symptoms are those of
a chronic systemic illness and include weight loss, fatigue, and dyspnea on
exertion.
|
|
|
|
FIGURE 10 Transverse
computed tomography of a 32-year-old patient with anterior and posterior
pericardial calcification (arrows). |
|
The
evaluation of chronic pericarditis should exclude the possibility of
tuberculosis; a tuberculin skin test, chest radiograph, and (when highly
suspicious) analysis of gastric aspirates should be performed. Pericardial
biopsy is more commonly diagnostic of tuberculous pericarditis than is
pericardial fluid staining or culture. Aggressive drug treatment is indicated.
Hypothyroidism-myxedema is another common cause of
large pericardial effusions, especially in the elderly. The effusion commonly
is identified first on a chest radiograph and often is seen in the absence of
resting tachycardia. Measurement of thyroid-stimulating hormone is diagnostic.
The effusion and coexistent cardiomyopathy respond to hormone replacement, but
sometimes slowly during several months. In the absence of hemodynamic
compromise, pericardiocentesis often is not needed in this situation as the
effusion has developed slowly and does not present hemodynamic compromise.
Uremic pericardial effusions also are common and often respond to initiation of
or more intensive dialysis.
Treatment
of chronic or recurrent idiopathic effusions is similar to the treatment of
recurrent pericarditis. If medical therapy is unsuccessful, creation of a
pericardial window is indicated.
CONSTRICTIVE PERICARDITIS
Constrictive
pericarditis is an uncommon condition with impairment of mid and late
ventricular filling from a thickened or noncompliant pericardium. In the
classic form, fibrous scarring and adhesions of both pericardial layers lead to
obliteration of the pericardial cavity. Early ventricular filling is unimpeded,
but diastolic filling subsequently is reduced abruptly as a result of the
inability of the ventricles to fill because of physical constraints imposed by
a rigid, thickened, and sometimes calcified pericardium. In less developed
countries, tuberculosis is the most common cause of chronic constrictive
pericarditis, whereas in the
Pathobiology
The
normal pericardium is
|
|
|
|
FIGURE 11 Right
atrial (RA) pressure recording from a patient with constrictive pericarditis.
Note the elevation in pressure and prominent y descent corresponding
to rapid early diastolic right atrial emptying. |
|
|
|
|
|
FIGURE 12 Simultaneous
left ventricular ( |
|
Clinical Manifestations
In
constriction, the most prominent physical finding is an abnormal jugular venous
pulse. Central venous pressure is elevated and displays prominent x and y
descents. For patients in sinus rhythm, the x descent is coincident with
the carotid pulse. The y descent, which is absent or diminished in
tamponade, is most prominent and abbreviated because of a rapid rise in
pressure in mid-diastole. A diagnosis of constriction always should be
suspected in patients with a prominent y descent with dyspnea, weakness,
anorexia, peripheral edema, hepatomegaly, splenomegaly, and ascites. The pulse
pressure is often narrowed, but pulsus paradoxus is usually absent. Pleural
effusions are common. The clinical picture may mimic hepatic cirrhosis, but
with distended neck veins. Venous pressure often fails to fall with inspiration
(Kussmaul's sign), and arterial pulse pressure is normal or reduced. The apical
pulse is often poorly defined, and heart sounds may be distant. A loud S3,
the pericardial knock, may be audible early after aortic valve closure because
of the sudden deceleration in ventricular filling.
Diagnosis
The
electrocardiogram of patients with constriction is often abnormal and displays
low QRS voltage (especially in the limb leads), P mitrale, and nonspecific ST-T
wave changes. Atrial fibrillation may be present in one third of patients. The
chest radiograph may show pericardial calcification in tuberculous
constriction. Though suggestive, the finding of pericar-dial calcification is
not diagnostic of constriction. Cardiac size may be small, normal, or enlarged.
Transthoracic echocardiography is less helpful than with cardiac tamponade, but
it may display pericardial thickening or calcification, abrupt posterior
deflection of the interventricular septum at end diastole, and M-mode posterior
wall “flat tiring.” Enhanced transmitral and transtricuspid Doppler E wave
variation with respiration may be particularly helpful in establishing the
diagnosis. The inferior vena cava and hepatic veins often are markedly dilated
with blunted respiratory variability in caval diameter. Newer tissue Doppler
imaging is also helpful to distinguish constrictive pericarditis from
restrictive
cardiomyopathy; constrictive pericarditis displays normal or enhanced early
diastolic indexes.
Increased
pericardial thickness is diagnosed most reliably by CT or MRI (see Fig. 10). CT
is more helpful for the identification of pericardial calcification. Right
atrial, inferior vena cava, and hepatic vein distention also are seen commonly
with CT and MRI. Like chest radiography, CT and MRI do not indicate the
physiologic significance of these anatomic findings and need to be interpreted
in the context of the clinical findings.
At
cardiac catheterization, patients with chronic constrictive pericarditis
usually have elevation (>
Treatment
|
Constrictive
pericarditis occasionally may reverse spontaneously when it develops in acute
pericarditis. More commonly, the natural history of this disease is one of progression
with declining cardiac output and progressive renal and hepatic failure.
Surgical stripping or removal of both layers of the adherent pericardium is
the definitive therapy. The benefits of pericardial stripping may be modest
initially but continue to be manifested in the ensuing months. Operative
mortality is generally low but may exceed 5 to 15% in the most advanced
cases. The surgical risk is related to the extent of myocardial involvement
and the severity of secondary hepatic or renal dysfunction. For patients with
suspected tuberculous constriction, antituberculosis therapy should be
administered before and after pericardial surgery. In addition to advanced
age and systolic dysfunction, postirradiation constriction is a predictor of
worse prognosis. |
Effusive-Constrictive
Pericarditis
Effusive-constrictive
pericarditis is a rare disorder occurring in about 1% of patients who have
pericarditis and approximately 7% of patients with tamponade. It is
characterized by the combination of a tense pericardial effusion in the
presence of visceral pericardial constriction and may represent an intermediate
stage in the development of constrictive pericarditis. Causes of
effusive-constrictive pericarditis are the same as those associated with
constriction, and the clinical features resemble those of tamponade and
constriction. Physical examination shows pulsus paradoxus and a prominent x
descent in the absence of a y descent. The cardiac silhouette is
generally enlarged because of the associated pericardial effusion, whereas the
electrocardiogram displays low QRS voltage and nonspecific ST-T wave changes.
Surface echocardiography may show an echo-filled pericardial effusion with
thickened pericardium and fibrinous pericardial bands. Although this echocardiographic
appearance should heighten suspicion, the diagnosis generally is made after
successful pericardiocentesis. Rather than normalizing after
pericardiocentesis, intracardiac pressures remain elevated with a square root
sign in the ventricular tracings and development of a prominent y
descent in the atrial and jugular venous pressure pulses. Kussmaul's sign also
may be evident. Treatment by excision of visceral and parietal pericardium is
usually effective. A transient, self-limited form of effusive-constrictive
pericarditis has also been reported.
Future Directions
Access
to the pericardial space may provide a new means to deliver novel gene or
pharmacologic therapies for myocardial (angiogenesis, antiarrhythmics) or
pericardial disease.
References:
A - Basic:
1. Davidson's Principles and
Practice of Medicine (1st
Edition) / Edited by N. R. Colledge, B. R. Walker, S. H. Ralston. - Philadelphia
2.
3.
Kumar and Clark's Clinical Medicine (8th
Revised edition) (With STUDENTCONSULT Online Access)
/ P.
KumarM. L. Clark, . –
B - Additional:
1. Braunwald's Heart Disease Review
and Assessment / L. S. Lilly. – Philadelphia
2.
3. Oxford Handbook of Cardiology2nd Revised
edition) / P. RamrakhaJ.Hill.
–
4.
Clinical Echocardiography (2 revised edition)
/ M. Y. Henein. -
5. Mayo Clinic Cardiology: Concise Textbook (4rd ed.) / by
Murphy J.G., Lloyd M.A., eds. – New York
6.
2011 ACCF/AHA
Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy
// Circulation. 2011; 124:
e783-e831
7. Web -sites:
http://emedicine.medscape.com/cardiology
http://meded.ucsd.edu/clinicalmed/introduction.htm