C h a p t e r 1 9
Disorders of Cardiac Function
469
outflow obstruction that is caused by systolic anterior
motion of the mitral valve and midsystolic contact with
the ventricular septum. The obstruction is worsened by
factors that increase myocardial contraction (e.g., sympa-
thetic stimulation or exertion) or decrease left ventricular
filling (e.g., Valsalva maneuver, peripheral vasodilation).
Clinical Manifestations.
The clinical manifestations of
HCM are highly variable and may progress to end-stage
heart failure with left ventricular remodeling and sys-
tolic dysfunction. The most frequent symptoms of HCM
are dyspnea and chest pain in the absence of coronary
artery disease. Syncope (fainting) is also common and
is typically post-exertional, when diastolic filling dimin-
ishes and outflow obstruction increases. Atrial fibrilla-
tion can occur as a long-term consequence of elevated
left atrial pressures. Ventricular arrhythmias are also
common and sudden death may occur, often in athletes
after extensive exertion. Risk factors for sudden cardiac
death among patients with HCM include a family his-
tory of syncope or sudden cardiac death, certain gene
mutations, and extreme hypertrophy of the left ventricle.
Diagnosis and Treatment.
Diagnosis of HCM is fre-
quently established with 2D echocardiography, ECG,
and continuous ambulatory monitoring. Cardiac MRI
can also be helpful. Genetic testing, through bidirectional
deoxyribonucleic acid (DNA) sequence analysis, is impor-
tant for identifying gene mutations and making diagno-
ses, although with some limitations.
48
In many patients
with HCM, physical examination results are normal.
Medical management of HCM is primarily focused
on symptom management. The first-line approach to
relief of symptoms is pharmacologic therapy designed
to block the effects of catecholamines that exacerbate
outflow obstruction and to slow heart rate to enhance
diastolic filling. In the majority of cases of symptomatic
HCM, beta blockers are the initial choice for therapy.
Calcium channel blockers, especially verapamil, can also
be used in patients who do not respond to beta block-
ers. Calcium channel blockers can, however, exacerbate
left ventricular outflow obstruction and are not recom-
mended for persons with severe outflow obstruction and
pronounced symptoms.
Dual-chamber and biventricular pacing may be used
to prevent progression of hypertrophy and obstruction.
In obstructive HCM that is refractory to drug therapy,
septal myotomy–myectomy (surgical excision of part of
the outflow myocardial septum) or alcohol ablation of
the interventricular septum can be used. An implant-
able cardioverter–defibrillator should be considered
for persons with HCM who have sustained ventricular
tachycardia or ventricular fibrillation and are receiving
optimal medical therapy.
46
Arrhythmogenic Right Ventricular Dysplasia
Arrhythmogenic right ventricular dysplasia (ARVD)
also called arrhythmogenic right ventricular cardio-
myopathy (ARVC), is a heart muscle disease that pri-
marily affects the right ventricle, leading to various
rhythm disturbances, particularly ventricular tachycar-
dia, and potentially to heart failure.
49
It ranks second,
after HCM, as the leading cause of sudden cardiac death
in young athletes. The incidence of ARVD varies from
about 1 in 2000 to 1 in 5000, affecting men more fre-
quently than women.
49
Arrhythmogenic right ventricular dysplasia is inherited
as an autosomal dominant trait in greater than 50% of
cases, although often with incomplete penetrance and vari-
able expression. Although multiple gene mutations have
been identified (mapping to chromosomes 1, 2, 3, 14, and
17),
50
the pathogenesis of the disorder remains undefined.
Clinical Manifestations.
The disorder is characterized
by progressive loss of myocytes, with partial or complete
replacement of the right ventricular muscle with adi-
pose or fibrofatty tissue. These changes are associated
with reentrant ventricular tachyarrhythmias of right
ventricular origin that are often precipitated by an exer-
cise-induced discharge of catecholamines. Clinical mani-
festations include palpitations, syncope, or cardiac arrest,
usually in young or middle-aged men. Other symptoms
may include abdominal pain and mental confusion.
Diagnosis andTreatment.
Diagnosis of ARVD is based
on clinical, ECG, echocardiographic, and histologic find-
ings. Personal and family history, including first- and
second-degree relatives, is important. Treatment for
ARVD is aimed at prevention of sudden cardiac death,
prevention or delay. Although ARVD cannot be cured, the
goal of treatment is to prevent and control the arrhyth-
mias with antiarrhythmic agents.
49
Radiofrequency abla-
tion may be used in cases that are refractory to drug
therapy, although it is completely successful in only
30% to 65% of cases, with multiple ablations some-
times needed. An implantable cardioverter–defibrillator
is also indicated for drug-refractory cases and for those
who have survived a sudden cardiac death episode. Final
options for treatment include ventriculotomy and heart
transplantation.
49
There are no randomized trials evalu-
ating ARVD treatment modalities at this time.
Dilated Cardiomyopathy
Dilated cardiomyopathy (DCM) is a common cause of
heart failure and the leading indication for heart trans-
plantation. Up to 35% of cases are reported as familial;
however, that proportion may be even higher, but due to
incomplete penetrance it is difficult to identify early or
latent disease in family members.
6,51
Most familial cases
appear to be transmitted as an autosomal dominant
trait, but autosomal recessive, X-linked recessive, and
mitochondrial inheritance patterns have been identified.
Other causes include infections (i.e., viral, bacterial,
fungal, mycobacterial, parasitic), toxins, alcoholism,
chemotherapeutic agents, metals, and multiple other
disorders. Often no cause is found, in which case it is
often referred to as idiopathic DCM.
Dilated cardiomyopathy is characterized by pro-
gressive cardiac dilation and contractile (systolic)
dysfunction, usually with concurrent hypertrophy.
6,51
