Cardiomyopathies

Cardiomyopathies are a group of diseases (three

major types) primarily involving the myocardium

and characterized by myocardial dysfunction that is
not the result of hypertension, coronary
atherosclerosis, valvular dysfunction, or pericardial
abnormalities.

Dilated

Ejection Fraction (normal >55%)

<30%

Left Ventricular Diastolic

Dimension (normal <55mm)

Left Ventricular Wall Thickness
Atrial Size
Valvular Regurgitation

60 mm

Common First Symptoms

Exertional intolerance

Congestive Symptoms
Risk for Arrhythmia

Decreased
Increased
Mitral first during decompensation; tricuspid

regurgitation in late stages

Left before right, except right prominent in

young adults
Ventricular tachyarrhythmia; conduction block

in Chagas' disease, giant cell myocarditis, and

some families; atrial fibrillation

Restrictive

Ejection Fraction (normal >55%)

25%-50%

--------------------------------------------- Left Ventricular Diastolic

---------------------------------------------- Dimension (normal <55mm)
----------------------------------------------- Left Ventricular Wall Thickness
--------------------------------------------

-------------------------------------------------- <60 mm
--------------------------------------------------- Normal or increased
--------------------------------------------------- Increased; may be massive
------------------------------------------------------- Frequent mitral and tricuspid regurgitation
---------------------------------------------------- Exertional intolerance
------------------------------------------------------ Right often exceeds left

Atrial Size

------------------------------------------------------------- Valvular Regurgitation

------------------------------------------------------------- Common First Symptoms
------------------------------------------------------------- Congestive Symptoms

Risk for Arrhythmia

Ventricular uncommon except in sarcoidosis; conduction

block in sarcoidosis and amyloidosis; atrial fibrillation

Hypertrophic
Ejection Fraction (normal >55%)

>60%

Left Ventricular Diastolic Dimension

(normal <55mm

Often decreased

Left Ventricular Wall Thickness

Markedly increased

Atrial Size

Increased

Valvular Regurgitation

Mitral regurgitation

Common First Symptoms*

Exertional intolerance; may have chest

pain

Congestive Symptoms*

Primary exertional dyspnea

Risk for Arrhythmia

Ventricular tachyarrhythmias
Atrial fibrillation

DILATED (CONGESTIVE)
CARDIOMYOPATHY

Definition
dilated cardiomyopathy, the heart is enlarged, and

both ventricles are dilated. Myocardial contractility

is diminished, and cardiac output is usually reduced

Etiology
Idiopathic
Familial
Alcoholism (accounts for 15 to 40% of all

cases in Western countries)

Collagen vascular disease (SLE, rheumatoid
arthritis, polyarteritis), dermatomyositis
Postmyocarditis
Peripartum (last trimester of pregnancy or 6
months postpartum)
Heredofamilial neuromuscular disease
Toxins (cobalt, lead, phosphorus, carbon
monoxide, mercury, doxorubicin,
daunorubicin) and possibly other trace
elements (mercury, antimony, gold,
chromium)
Nutritional (beri-beri, selenium deficiency,
carnitine deficiency, thiamine deficiency)
Cocaine, heroin, organic solvents ("glue
sniffer's heart")
Irradiation
Acromegaly, osteogenesis imperfecta,
myxedema, thyrotoxicosis, diabetes

Hypocalcemia
Antiretroviral agents (zidovudine,

didanosine, zalcitabine)

Phenothiazines
Infections: viral (human immunodeficiency

virus, coxsackievirus B), rickettsial,

mycobacterial, toxoplasmosis, trichinosis,
Chagas' disease, bacterial
Hematologic (e.g., sickle cell anemia,
hemochromatosis)
Ischemic
Heat stroke
Amyloid
End-stage renal disease on hemodialysis
Prolonged tachycardia
Takotsubo cardiomyopathy (secondary to
severe stress or vigorous exercise)

Idiopathic dilated cardiomyopathy is often familial,

and apparently healthy relatives may have latent,

early, or undiagnosed established disease.
Echocardiographic evaluation of family members is
recommended.

Prognosis
Annual mortality rate is 20% in patients with

moderate heart failure, and it exceeds 50% in

patients with severe heart failure. Patients with
peripartum cardiomyopathy have a better prognosis
than do those with cardiomyopathy due to
infiltrative myocardial disease, HIV infection, or
doxorubicin therapy.

Symptoms
Dyspnea on exertion, orthopnea, paroxysmal

nocturnal dyspnea
Fatigue
Palpitations
Systemic and pulmonary embolism
Chest pain
Resting tachycardia

Physical Findings
Resting tachycardia
Increased jugular venous pressure
Small pulse pressure
Pulmonary rales, hepatomegaly, peripheral edema
S3, S4
Mitral regurgitation, tricuspid regurgitation (less

common)

Diagnostic Studies
Chest x-ray:

Massive cardiac enlargement

Interstitial pulmonary edema

ECG:

Left ventricular hypertrophy with ST-T wave changes

Right bundle branch block (RBBB) or LBBB
P wave changes indicative of left atrial abnormalities, firstdegree AV block
Arrhythmias (sinus tachycardia, atrial fibrillation, PVC,
premature atrial contraction, ventricular tachycardia)

Diagnostic Studies
Echocardiogram: chamber enlargement, low EF with

global akinesia
Cardiac catheterization: elevation of left or right
ventricular end-diastolic pressures; cardiac output is
generally normal or reduced and does not rise
significantly with exercise. Biopsy is helpful in
dilated cardiomyopathy to look for potentially
treatable causes (e.g., sarcoidosis, hemochromatosis)
and to establish a definitive diagnosis (e.g.,
amyloidosis).

Diagnostic Studies
The role of endomyocardial biopsy in patients with

dilated cardiomyopathy is not well defined.

Diagnostic yield is generally low, and the risks of
occasional perforation and death further limit its
use.

Therapy
Treat underlying disease (SLE, alcoholism,

hemochromatosis).
Treat CHF (cause of death in 70% of patients) with
sodium restriction, diuretics, ACE inhibitors, blockers, spironolactone, and digitalis .
Limit activity when CHF is present.

Therapy
Vasodilators (combined with nitrates and ACE

inhibitors) are effective on all symptomatic patients

with left ventricular dysfunction.
Prevent thromboembolism with oral anticoagulants
in all patients with atrial fibrillation and in patients
with moderate or severe failure.

Therapy
Low-dose -blockade with carvedilol or other -

blockers may improve ventricular function by

interrupting the cycle of reflux sympathetic activity
and controlling tachycardia.

Therapy
Diltiazem and ACE inhibitors have been reported to

have a long-term beneficial effect in patients with

idiopathic dilated cardiomyopathy.

Therapy
Use antiarrhythmic treatment as appropriate.

Empiric pharmacologic suppression of asymptomatic

ventricular ectopy does not reduce risk for sudden
death or improve long-term survival. In patients
with severe left ventricular dysfunction and/or
symptomatic and sustained ventricular tachycardia,
the use of an automatic, implantable cardioverterdefibrillator should be considered.

Therapy
Growth hormone administration has been shown to

increase myocardial mass and reduce the size of the

left ventricular chamber, resulting in improvement
in hemodynamics and clinical status. This
therapeutic approach remains controversial.

Therapy
Patients with dilated cardiomyopathy (left

ventricular EF <25%) and associated coronary

atherosclerosis (angina, ECG changes, reversible
defects on thallium scan) may benefit from surgical
revascularization.
Consider heart transplant for young patients
(younger than 60 years of age) who are no longer
responsive to medical therapy.

RESTRICTIVE
CARDIOMYOPATHY

Definition
Restrictive cardiomyopathy is characterized by

decreased ventricular compliance, usually secondary

to infiltration of the myocardium. These patients
have impaired ventricular filling and reduced
diastolic volume, normal systolic function, and
normal or near-normal myocardial thickness.

Etiology
Infiltrative and storage disorders (glycogen storage disease,

amyloidosis, sarcoidosis, hemochromatosis)

Scleroderma
Radiation
Endocardial fibroelastosis
Endomyocardial fibrosis
Idiopathic: many patients classified as having "idiopathic"
restrictive cardiomiopathy may have mutations in the gene for
cardiac troponin I and restrictive cardiomyopathy may represent an
overlap with hypertrophic cardiomyopathy in many familial cases.
Toxic effects of anthracycline
Carcinoid heart disease, metastatic cancers
Diabetic cardiomyopathy
Eosinophilic cardiomyopathy (Lffler's endocarditis)

Symptoms and Physical

Restrictive cardiomyopathy presents with symptoms

of progressive left-sided and right-sided heart

failure:

Edema, ascites, hepatomegaly, distended neck veins may be

present.
Fatigue, weakness (secondary to low output) are common.
Kussmaul's sign may be present.
Regurgitant murmurs are common.
Apical impulse may be prominent.
An early diastolic third heart sound is often heard.

Diagnostic Studies
Chest x-ray:

Moderate cardiomegaly
Possible evidence of CHF (pulmonary vascular congestion, pleural effusions)

ECG:

Low voltage with ST-T wave changes.

Frequent arrhythmias, left-axis deviation, and atrial fibrillation may be present.

Echocardiogram reveals increased wall thickness and thickened cardiac valves (especially in

patients with amyloidosis).

Cardiac catheterization: to distinguish restrictive cardiomyopathy from constrictive
pericarditis.

Constrictive pericarditis: usually involves both ventricles and produces a plateau of elevated filling pressures.

PCWP equal to right atrial pressure and right ventricular end-diastolic pressure.
Pulmonary artery systolic pressure <50 mm Hg.
Right ventricular end-diastolic pressure greater than one third the right ventricular systolic pressure.

Restrictive cardiomyopathy: impairs the left ventricle more than the right.

PCWP greater than right atrial pressure.

Pulmonary artery systolic pressure > 50 mm Hg.

Magnetic resonance imaging (MRI) can assess the extent of pericardial thickening and may be

useful in distinguishing restrictive cardiomyopathy from constrictive pericarditis (thickness of

the pericardium is 5 mm in the latter).

Therapy
Cardiomyopathy caused by hemochromatosis may respond to

repeated phlebotomies to decrease iron deposition in the

heart.
Sarcoidosis may respond to corticosteroid therapy.
Corticosteroid and cytotoxic drugs may improve survival in
patients with eosinophilic cardiomyopathy.
There is no effective therapy for other causes of restrictive
cardiomyopathy. Death usually results from CHF or
arrhythmias; therefore, therapy should be aimed at
controlling CHF by restricting salt, administering diuretics,
and treating potentially lethal arrhythmias. Cardiac
transplantation can be considered in patients with refractory
symptoms in idiopathic or familial restrictive
cardiomyopathies.

HYPERTROPHIC
CARDIOMYOPATHY

In hypertrophic cardiomyopathy (HCM), there is

marked hypertrophy of the myocardium and

disproportionately greater thickening of the
interventricular septum than that of the free wall of
the left ventricle (asymmetric septal hypertrophy).

Pathophysiology
During midsystole, the apposition of the anterior

mitral valve leaflet against the hypertrophied septum

can cause narrowing of the subaortic area and result
in left ventricular outflow obstruction; because of
this, the disease has been called idiopathic
hypertrophic subaortic stenosis or hypertrophic
obstructive cardiomyopathy. Patients with
hypertrophic cardiomyopathy also have limited
ability to dilate the coronary arteries in response to
increased myocardial oxygen demand.

Epidemiology
The disease occurs in two major forms: A familial

form, usually diagnosed in young patients and genemapped to chromosome 14q. Autosomal dominant
trait with variable penetrance caused by mutations in
any of 1 to 10 genes, each encoding proteins of
cardiac sarcomere
A sporadic form, usually found in elderly patients.

Factors Influencing Obstruction

Increase Obstruction _:

Drugs: digitalis, -adrenergic stimulators (isoproterenol, dopamine,

epinephrine), nitroglycerin, vasodilators, diuretics, and alcohol
Hypovolemia
Tachycardia
Valsalva maneuver
Standing position

Decrease Obstruction Drugs:

-adrenergic blockers, calcium channel blockers, disopyramide, adrenergic stimulators (phenylephrine)

Volume expansion
Bradycardia
Handgrip exercise
Squatting position

Symptoms
Hypertrophic cardiomyopathy may be suspected on

the basis of abnormalities found on physical

examination.
Classic findings include:

Dyspnea
Syncope (usually seen with exercise)
Angina (decreased angina in recumbent position)
Palpitations
Sudden death: may be the only manifestation (usually seen in
young adults during physical exercise)

Physical Findings
Harsh, systolic, diamond-shaped murmur at the left

sternal border or apex that increases with Valsalva

maneuver and decreases with squatting
Paradoxic splitting of S2 (if left ventricular
obstruction is present)
S4
Double or triple apical impulse
Very rapid and forceful carotid upstroke (percussion

wave)

Diagnostic Studies
Chest x-ray: normal or cardiomegaly
ECG is abnormal in 75% to 95% of patients
Left ventricular hypertrophy
Abnormal Q waves may be seen in anterolateral and inferior leads
Two-dimensional echocardiography is used to establish the diagnosis. Findings

include:

Ventricular hypertrophy
Ratio of septum thickness to left ventricular wall thickness greater than 1.3:1
Increased EF
Mitral regurgitation

MRI may be of diagnostic value when echocardiographic studies are technically

inadequate. MRI is also useful in identifying segmental LVH undetectable by

echocardiography.
Cardiac catheterization:

Elevated left ventricular end-diastolic pressure

Increased height of left atrial A wave
Pressure gradient between left ventricle and aorta
Small hyperdynamic left ventricle
Mitral regurgitation

Treatment
Therapy for hypertrophic cardiomyopathy is directed

at blocking the effect of catecholamines that can

exacerbate dynamic left ventricualr outflow tract
obstruction and avoidance of certain agents (e.g.,
vasodilators or diuretic agents), which can worsen
the obstruction.

Propranolol 160 to 320 mg/d. The beneficial effects

of -blockers on symptoms (principally dyspnea and

chest pain) and exercise tolerance appear to be due
largely to a decrease in the heart rate with
consequent prolongation of diastole and increased
passive ventricular filling. By reducing the inotropic
response, -blockers may also lessen myocardial
oxygen demand and decrease the outflow gradient
during exercise, when sympathetic tone is increased.

Verapamil also decreases left ventricular outflow

obstruction by improving filling and probably

reducing myocardial ischemia.
Intravenous saline solution infusion in addition to
propranolol or verapamil is indicated in patients
with CHF.

24-hour Holter monitoring is used to screen for

potentially lethal arrhythmias (principal cause of

syncope or sudden death in obstructive
cardiomyopathy).

Implantable defibrillator is a safe and effective therapy in

patients who are prone to ventricular arrhythmias.
Electrophysiologic studies may be used to select prophylactic
therapy.
Disopyramide is a useful antiarrhythmic, because it is also a
negative inotrope.

Surgical treatment (myotomy-myectomy) is reserved

for patients who have both a large outflow gradient

( 50 mm Hg) and severe symptoms of heart failure
that are unresponsive to medical therapy. The risk
for sudden death from arrhythmias is not altered by
surgery.

Implantable defibrillators are a safe and effective

therapy in HCM patients prone to ventricular

arrhythmias. Their use is strongly warranted for
patients with previous cardiac arrest or sustained
spontaneous ventricular tachycardia. Implantation
of a dual chamber pacemaker has not been shown to
result in significant improvement in objective
measures of exercise capacity.

Antibiotic prophylaxis for bacterial endocarditis for

surgical procedures.
Screening of first-degree relatives with two-dimensional
echocardiography is indicated.
Avoid use of digitalis, diuretics, nitrates, and
vasodilators.
Avoidance of alcohol; alcohol use (even in small
amounts) results in increased obstruction of the left
ventricular outflow tract.
Encouraging results have been reported on the use of
pacing for hemodynamic and symptomatic benefit in
patients with drug-resistant hypertrophic obstructive
cardiomyopathy.

Prognosis
Patients with HCM are at increased risk for sudden

death, especially if the onset of symptoms is during

childhood. Ventricular tachycardia or fibrillation
appears to be the principal mechanism of sudden
death in these patients. In high-risk patients with
hypertrophic cardiomyopathy, implantable
defibrillators are highly effective in terminating such
arrhythmias and may have a significant role in the
primary and secondary prevention of sudden death.

Prognosis
Adult patients can be considered low risk if they

have no symptoms or mild symptoms and also if they

have none of the following:

A family history of premature death due to HCM

Nonsustained ventricular tachycardia during Holter
monitoring
A marked outflow tract gradient
Substantial left ventricular hypertrophy (>20 mm)
Marked left atrial enlargement
Abnormal blood-pressure response during exercise
Recurrent syncope

Left ventricular outflow tract obstruction at rest is a

strong, independent predictor of progression to

severe symptoms of heart failure and of death.

Screening
Screening of first-degree relatives with two-

dimensional echocardiography and

electrocardiography is indicated, particularly if
adverse HCM-related events have occurred in the
family. Annual screening is recommended for all
adolescents aged 12 to 18. Periodic screening of all
first-degree adult family members at 5-year intervals
is recommended because hypertrophy may not be
detected until the sixth decade of life. It is advisable
to have a trained clinical genetic counselor see the
patient and obtain consent before genetic testing.

Screening
Future screening techniques may involve

identification of mutations in the gene encoding the

sarcomeric proteins. The most common sarcomeric
subtype is MYBPC3-HCM, affecting one in five
patients. Clinical predictors of positive genotype,
such as the need for an implantable cardioverterdefibrillator, young age at diagnosis, high degree of
left ventricular wall hypertrophy, and family history
of HCM, may aid in patient selection for genetic
testing and increase the yield of cardiac sarcomere
gene screening.