Cardiomyopathies

V. Cardiomyopathies
A. Dilated (congestive) cardiomyopathy
1. Definition. Dilated cardiomyopathy is defined as a diminution in the contractile function of the left, right, or both ventricles in the absence of pressure overload, volume overload, or coronary artery disease. The loss of cardiac muscle function results in CHF.
2. Etiology. The cause of most cases of dilated cardiomyopathy is unknown. Viral infection has been implicated in the pathogenesis of this disease, but proof of cause generally is lacking. The following other conditions have been linked to cardiomyopathy.
a. Prolonged ethanol abuse is the most common reversible cause of cardiomyopathy.
b. Doxorubicin therapy. High doses of doxorubicin, a commonly used chemotherapeutic drug, may result in irreversible dilated cardiomyopathy.
c. Exposure to mercury, lead, or high-dose catecholamines may cause myocardial damage and dilated cardiomyopathy.
d. Endocrinopathies, including thyrotoxicosis, hypothyroidism, and acromegaly, have been reported to cause dilated cardiomyopathy. In thyrotoxicosis and in hypothyroidism, the myopathy usually is reversed when the endocrinopathy is corrected.
e. Metabolic disorders (e.g., hypophosphatemia, hypocalcemia, thiamin deficiency) may produce reversible cardiomyopathy.
f. Hemoglobinopathies (e.g., sickle cell anemia, thalassemia) are associated with myocardial dysfunction.
g. Genetic abnormalities. In some families, the development of dilated cardiomyopathy is linked to specific genetic abnormalities.
h. Prolonged tachycardia (persisting for weeks or months) may result from uncontrolled atrial arrhythmias, causing a dilated cardiomyopathy that may be reversed within weeks, after heart rate is controlled.
3. Clinical features, diagnosis, and treatment of dilated cardiomyopathy are similar to left- and right-sided CHF as described in I D–F.
a. a. Symptoms of dilated cardiomyopathy are those of both left- and right-sided CHF as described in I D 1.







(1) Generally, the symptoms of left-sided failure (i.e., orthopnea, paroxysmal nocturnal dyspnea, and dyspnea on exertion) precede those of right-sided failure.
(2) Chest pain may occur in the absence of obstructive coronary disease. The cause of the chest pain may be the excessive oxygen demands of an enlarged, thin-walled ventricle with high wall stress.
b. Physical signs in dilated cardiomyopathy are those of CHF. A gallop rhythm is usually present. The murmur of mitral regurgitation also may be present. Mitral regurgitation occurs as a result of ventricular dilation and improper alignment of the papillary muscles.

4. Diagnosis

a. Electrocardiography reveals frequent left ventricular hypertrophy and nonspecific ST- and T-wave abnormalities. Left bundle branch block is common.
b. Chest radiography shows an enlarged heart, and there is evidence of pulmonary vascular congestion.
c. Echocardiography reveals dilated and poorly contracting left and right ventricles. In addition, secondary left and right atrial enlargement usually is seen.
d. Gated blood pool scanning in dilated cardiomyopathy reveals reduction of the ejection fraction of both ventricles. There usually is global dysfunction, but regional contractile abnormalities also may exist.
e. Cardiac catheterization usually is not necessary to make the diagnosis of dilated cardiomyopathy. However, because surgical correction of ischemic heart disease can occasionally improve left ventricular function, ischemic heart disease should be excluded prior to making the diagnosis of cardiomyopathy. In such cases, cardiac catheterization may be indicated.
5. Therapy

a. Removal of an offending agent. The most hopeful situation is one in which incessant tachycardia or a known toxin has caused ventricular dysfunction. Heart rate control or removal of the toxin from the patient's environment may lead to significant improvement in ventricular function.
b. Supportive therapy. When dilated cardiomyopathy is idiopathic, the symptoms of CHF can be improved by such measures as salt restriction and administration of cardiac glycosides, diuretics, vasodilators, and neurohumoral blockers. Evidence shows that the addition of ACE inhibitors to a standard regimen of diuretics increases longevity. Gradual introduction of خ²-blockers also prolongs life.
c. Cardiac transplantation. Cardiac transplantation may offer an improved quality of life to selected patients when control of CHF is not possible and prognosis is poor.
B. Hypertrophic cardiomyopathy
1. Definition. Hypertrophic cardiomyopathy is a disorder in which regional hypertrophy of the left ventricle occurs independent of loading conditions. It most commonly involves the interventricular septum, but can also involve the apex. When the septum is involved, the hypertrophied septum and the anterior leaflet of the mitral valve may produce dynamic left ventricular outflow obstruction.
2. Etiology. Most cases are inherited through an autosomal dominant mode of transmission, but sporadic cases also occur. Specific abnormalities in the genes coding for cardiac myosin and other cardiac proteins have been identified.
3. Pathophysiology
a. Methods of obstruction include the following:
(1) As shown in Figure 1-10, the hypertrophied septum encroaches on the left ventricular outflow tract and comes into close approximation with the anterior leaflet of the mitral valve.

FIGURE 1-10 Cardiac cross-section cut from the apex to the base in a patient with hypertrophic obstructive cardiomyopathy. The upper portion of the septum is thickened and comes into close proximity with the anterior leaflet of the mitral valve. (Adapted from Johnson R, et al. The Practice of Cardiology. Boston: Little, Brown, 1980:648.)





(2) During systole, a low-pressure zone may develop as blood flow accelerates through the narrowed area between the septum and the anterior leaflet, generating a Bernoulli effect. Thus, the anterior leaflet of the mitral valve is drawn into the septum (systolic anterior motion), leading to outflow obstruction.
(3) The septum itself shortens very little during systole because of its catenoid shape. Because the septum does not shorten, it cannot thicken. Therefore, it is the anterior leaflet of the mitral valve that plays the active role in creating the obstruction.
b. The degree of outflow obstruction varies from patient to patient and from time to time in the same patient.
(1) Physiologic conditions that enlarge the left ventricle (e.g., increases in preload and afterload) separate the septum and anterior leaflet of the mitral valve and reduce the obstruction.
(2) Physiologic conditions that make the ventricle smaller or that increase the velocity of blood flow (e.g., dehydration, positive inotropic drugs) increase the degree of obstruction.
c. The obstruction to outflow may cause secondary cardiac hypertrophy of the nonseptal portions of the ventricle, but septal thickness generally remains greater than that of the free wall of the ventricle.
4. Clinical features
a. Symptoms
(1) Angina. Patients with obstructive cardiomyopathy frequently complain of chest pain.
(a) The pain usually has atypical features; that is, the pain may occur at rest and is not always related to exercise.
The pathophysiology of angina in hypertrophic obstructive cardiomyopathy is unclear, but coronary blood flow is subnormal, potentially causing ischemia.
(2) Syncope
(a) Syncope usually occurs during or after exercise in patients with obstructive cardiomyopathy as a result of reduced left ventricular size and the consequent increased obstruction to outflow.
(i) After exercise, afterload is reduced because of peripheral vasodilation.
(ii) Preload is reduced because of the decreased activity of the contractions of the leg muscles, which help to return blood to the heart.
(iii) The inotropic state remains elevated because of the increased catecholamine level after exercise.





(b) Arrhythmias, which are common in this disorder, also may precipitate syncope or sudden death.
(3) CHF. Dyspnea on exertion, orthopnea, and paroxysmal nocturnal dyspnea occur in patients with obstructive cardiomyopathy. Systolic function usually is normal or supranormal, and the ejection fraction often exceeds 80%.
(a) The symptoms of heart failure usually are not caused by systolic malfunction, but rather occur as a result of increased diastolic stiffness.
(b) The thickened myocardium requires an increased filling pressure for adequate diastolic distention. The increased filling pressure is reflected to the lungs and produces pulmonary congestive symptoms.
(c) In the later stages of the disease, however, systolic dysfunction also may occur, contributing to the symptoms of CHF.
b. Physical signs
(1) Carotid upstroke. In patients with the obstructive form of the disease, the carotid upstrokes have a spike and dome character (Online Figure 1-11). This configuration indicates early systolic outflow followed by a period of obstruction, during which flow falls. The dome portion of the curve reflects the period near the end of systole when obstruction diminishes and aortic outflow again commences.


ONLINE FIGURE 1-11 Diagram showing simultaneous recording of the electrocardiogram (ECG), left ventricular pressure tracing (LV), and aortic pressure tracing (Ao) in a patient with hypertrophic obstructive cardiomyopathy. A large pressure gradient exists between the left ventricle and aorta. The aortic pressure tracing (similar to the carotid pulse) demonstrates a spike and dome configuration. (Reprinted from Cohn PF, Wynne J. Diagnostic Methods in Clinical Cardiology. Boston: Little, Brown, 1982:147, with permission.)

(2) Murmur. The murmur is a systolic ejection murmur heard along the left sternal border. Unlike the murmur in aortic stenosis, it does not usually radiate to the neck.
(a) Increasing the intensity of the murmur
(i) Maneuvers that diminish left ventricular size cause an increase in both the obstruction to outflow and the intensity of the cardiac murmur. Thus, the Valsalva maneuver, which diminishes the murmur in valvular aortic stenosis by diminishing flow, increases the murmur in obstructive cardiomyopathy by increasing obstruction.
(ii) Having the patient stand or inhale amyl nitrite also diminishes left ventricular size and therefore increases the intensity of the murmur.
(b) Diminishing the intensity of the murmur. Squatting, which increases myocardial afterload and venous return to the heart, increases cardiac size and, therefore, diminishes the murmur.
5. Diagnosis
a. Electrocardiography almost always is abnormal. The ECG usually shows evidence of left ventricular hypertrophy, nonspecific ST- and T-wave abnormalities, and left atrial enlargement.
b. Echocardiography establishes the diagnosis in most patients.
(1) In patients with asymmetric septal hypertrophy without obstruction, increased septal thickness results in a septum-to-free wall thickness ratio of 1.3:1 or greater.
(2) Findings in the obstructive form of the disease include systolic anterior motion of the mitral valve, systolic fluttering of the aortic valve leaflets, and early closure of the aortic valve, corresponding to the spike and dome seen in the carotid pulse.
6. Therapy. Unlike aortic stenosis, in which relief of valvular obstruction relieves symptoms and prolongs life, there is no conclusive evidence that surgical relief of obstruction in obstructive cardiomyopathy prolongs life. Therefore, medical therapy is used first in an attempt to improve symptoms.
a. Medical therapy
(1) خ²-blockers are effective in relieving symptoms in this disease.
(a) خ²-blockade slows the heart rate, which increases left ventricular filling and size, diminishing obstruction.
(b) خ²-blockade also reduces the vigor of left ventricular contraction and, thus, decreases the velocity of blood flow, which also reduces the degree of obstruction.
(2) Calcium channel blocking agents. These agents are an alternative to خ²-blockers and have been shown to diminish the left ventricular outflow gradient. Verapamil is the calcium channel blocker most widely used in the treatment of this disease. Caution must be exercised in patients with CHF because verapamil may worsen failure and precipitate acute pulmonary edema.








(3) Digitalis is contraindicated in the hyperdynamic phase of the disease when obstruction is present and the left ventricular cavity is small, because digitalis increases the vigor of left ventricular contraction and thus increases the outflow obstruction.
b. Surgical therapy
(1) Myomectomy. Surgical reduction of the thickness of the left ventricular septum relieves the outflow gradient and symptoms in those patients who have not responded to medical therapy.
(2) Mitral valve replacement. Because it is the anterior leaflet of the mitral valve that produces the obstruction, mitral valve replacement is also effective in relieving obstruction.
(3) Intentional septal infarction. Transcatheter instillation of ethanol into the septal artery is performed to infarct the septum and reduce obstruction.
c. Antiarrhythmic therapy. Most patients with hypertrophic myopathy die suddenly. Patients with a family history of sudden death or a personal history of syncope or ventricular tachycardia are at high risk and should undergo electrophysiologic testing. Many patients receive implantable defibrillators.
C. Restrictive cardiomyopathy
1. Definition. The restrictive cardiomyopathies are a group of diseases in which the composition of the myocardium has changed so that it becomes stiffer. The increased stiffness of the myocardium restricts left ventricular filling, thereby reducing stroke output and increasing left ventricular filling pressure.
2. Etiology. Infiltrative diseases of the myocardium, which produce restrictive cardiomyopathy, include amyloidosis, hemochromatosis, idiopathic eosinophilia, carcinoid syndrome, sarcoidosis, and endomyocardial fibroelastosis.
3. Pathophysiology. Systolic function usually is normal in the early stages of the disease, but the altered properties of the myocardium increase diastolic stiffness. Thus, the left ventricular pressure is above normal at any diastolic left ventricular volume. Increased filling pressure produces pulmonary congestion. As the infiltrative process progresses, systolic function also is compromised.
4. Clinical features
a. Symptoms of both left-sided and right-sided CHF usually are present; the symptoms of right-sided failure are usually more prominent.
b. Physical signs include those present in left-sided and right-sided CHF.
5. Diagnosis
a. Electrocardiography. The ECG frequently shows low QRS voltages and nonspecific ST- and T-wave abnormalities. Conduction abnormalities are common.
b. Radiographs. Signs of pulmonary vascular congestion may coexist with normal heart size, because even when left ventricular systolic function fails in the later stages of the disease, the restriction to cardiac filling prevents cardiac dilation.
c. Echocardiography
(1) The echocardiogram may demonstrate thickening of the left and right ventricles. The combination of increased left ventricular thickness on the echocardiogram and decreased left ventricular voltage on the ECG is highly suggestive of restrictive cardiomyopathy.
(2) Doppler examination may reveal evidence of abnormal ventricular diastolic filling or altered compliance.
(3) Left and right ventricular chamber sizes usually are normal, whereas the left and right atria are increased in size.
(4) In amyloidosis, the myocardium may appear brighter than normal.
d. Cardiac catheterization. Often it is difficult to distinguish restrictive cardiomyopathy from constrictive pericarditis.
(1) A dip and plateau in the left and right ventricular filling pressures may be seen in both diseases.
(2) In restrictive cardiomyopathy, left and right atrial pressures and left and right ventricular filling pressures usually are not identical, as they are in constrictive pericarditis.
(3) Endomyocardial biopsy during cardiac catheterization may help establish the diagnosis.
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6. Therapy. Treatment for this group of diseases is limited.
a. In cases with a reversible etiology (e.g., hemochromatosis), direct therapy such as iron chelation may result in improvement.
b. When the cause of the disease cannot be treated, symptomatic therapy with diuretics to reduce the symptoms of congestion is indicated.