Paul Gordon, MD
Douglas Burtt, MD
with special thanks to the late Abdul Hakim Khan, M.D.

CARDIOMYOPATHIES
 

DEFINITIONS AND CLASSIFICATION (Table 1)

Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force defines cardiomyopathies as diseases of the myocardium associated with cardiac dysfunction. They are classified into dilated, hypertrophic, restrictive or arrhythmogenic right ventricular dysplasia. Although this classification is useful and practical, there is significant heterogeneity amongst the classes such that one form may also show subtle features of the other form or forms. Classification is based on clinical features, investigations (mainly echocardiography), myocardial biopsy or necropsy studies.

GENERAL FEATURES (Table 2)

Characteristics of dilated cardiomyopathy include dilation of cardiac chambers and diminished systolic function of the left ventricle or both ventricles. Ventricular end diastolic pressure or filing pressure is near normal at low volumes but becomes elevated at high diastolic volumes as further dilation encroaches on the myocardium rendered non-compliant by hypertrophy, fibrosis or ischemia. Ejection fraction is reduced and may become progressively worse with time. In hypertrophic cardiomyopathy ventricular size is normal but ventricular walls (especially interventricular septum) are markedly hypertrophied. Systolic function and ejection fraction are normal but end diastolic pressure is elevated because of reduced compliance. In restrictive cardiomyopathy cardiac chambers are normal in size or mildly dilated. Wall thickness is mildly increased. Systolic function is usually normal but diastolic pressure is elevated because of non-compliant walls due to fibrosis or infiltrative processes. Ejection fraction, is essentially normal. Note that left ventricular diastolic pressure and therefore pulmonary capillary pressure is elevated in all three types of cardiomyopathies (albeit through different mechanisms) leading to pulmonary congestion.

DILATED CARDIOMYOPATHY

ETIOLOGY (Table 3)

Although most cases of dilated cardiomyopathy are idiopathic, several etiologies have been implicated in the pathogenesis of dilated cardiomyopathy. In addition recent studies have indicated that some people are genetically predisposed to the development of idiopathic cardiomyopathy and this may explain some of the familial forms of dilated cardiomyopathy.

VIRUSES

Viruses, especially those belonging to picornavirus group such as Cox B, A and echoviruses are known to cause myocarditis. Myocardial biopsy studies have demonstrated the presence of virus in

myocytes during acute myocarditis. Some of the patients with myocarditis go on to develop cardiomyopathy. The latter results from an autoimmune response since no viruses can be demonstrated in this stage and also because histologic examination shows changes consistent with an immune response i.e. macrophages and T-lymphocytes. It is also very likely that a few cases of "idiopathic" cardiomyopathy are viral in etiology.

PERIPARTUM

Unexplained heart failure occurring in a previously healthy woman in the last month of pregnancy or within 5 months of delivery is known as peripartum cardiomyopathy. It is more commonly encountered in women over the age of 30, and in multiparous women. The etiology remains unknown although viral myocarditis, cardiac injury from prolonged exposure to high levels of catecholamine during pregnancy and nutritional factors have been implicated. Ideally these patients should be advised against future pregnancy because of the risk of recurrence of severe heart failure.

ANTHRACYCLINE induced cardiomyopathy is usually dose dependent and its adverse effects often persist despite discontinuation of treatment. Metabolites of anthracyclines produce free radicals. Heart muscle lacks free radical detoxifying properties. Free radicals promote extensive calcium release and depletion of sarcoplasmic reticulum calcium stores and lead to impaired contractility and relaxation.

COCAINE

It is estimated that as many as 5 million Americans use cocaine regularly. The most common cardiovascular complications of cocaine are angina, myocardial infarction and arrhythmias including cardiac arrest. Dilated cardiomyopathy is a rare complication of cocaine.

CHRONIC ALCOHOLISM

Chronic alcoholism produces cardiomyopathy in some predisposed individuals. It is unclear whether the damage to the heart muscle is due to metabolites of alcohol such as acetaldehyde or some other cause such as immune mediated injury. Its importance lies in early detection; total abstinence usually results in cure.

ISCHEMIC

Significant coronary artery disease and progressive dilation of heart following infarction (remodeling) may ultimately lead to systolic LV dysfunction - ischemic cardiomyopathy.

OTHER CAUSES

Infection with bacteria (Lyme disease - Borelia burgdorfei), Chagas disease (Trypanosoma cruzi) diabetes and other endocrinopathies, collagen vascular diseases (e.g. lupus erythematosis) nutritional factors (selenium deficiency) etc. are other potential causes of dilated cardiomyopathies. In addition late stage valvular disease, hypertensive heart disease, renal failure may present as dilated cardiomyopathy. Uncontrolled ventricular rate in patients with atrial fibrillation as well as other forms of tachyarrhythmias predispose patients to the risk of a form of dilated cardiomyopathy known as tachycardia cardiomyopathy; it can be reversed with control of heart rate.

PATHOLOGY

The heart is enlarged and the cardiac mass is increased; cardiac chamber dilation is out of proportion to the ventricular wall hypertrophy i.e. volume/mass ratio is increased. Enlarged chambers and poor contractility cause stagnation of blood and lead to the formation of intracardiac blood clots and predisposes patients to thromboembolic complications, e.g. stroke.

Heart muscle shows nonischemic changes of hypertrophy interspersed with areas of scar formation - fibrosis and atrophy. Specific histologic picture may be noted in patients with collagen vascular disease (e.g. lupus), amyloid, etc.

PATHOPHYSIOLOGY (Table 4A, Table 4B)

In the early stages, compensatory mechanisms (i.e. neurohormonal) help to maintain cardiac output. Subsequently, with progressive myocardial damage from primary pathology as well as from the increased activity of compensatory mechanisms, heart dilates, systolic function deteriorates and cardiac output as well as ejection fraction decreases. There is also mild compensatory hypertrophy of ventricular walls. Enlargement of ventricles results in papillary muscle dysfunction and dilation of mitral and tricuspid rings leading to mitral and tricuspid regurgitation. Regurgitation of valves aggravates heart failure. Dilation of atria and fibrotic changes in atrial muscles often provokes atrial fibrillation further increasing the risk of heart failure and thromboembolic complications.

CLINICAL FEATURES

History (Table 5)

A flu-like illness followed a few weeks later with heart failure should lead one to suspect viral etiology as the cause of cardiomyopathy. In other cases there may be a history of pregnancy, chronic alcohol abuse, history of anthracycline treatment, etc. Most cases of dilated cardiomyopathy seek medical attention for symptoms of congestive heart failure, others are seen because of new onset of cardiac arrhythmia or manifestations of an embolic event such as a stroke.

PHYSICAL EXAMINATION (Table 6)

Physical examination of a patient with dilated cardiomyopathy would depend on the stage of the disease and would therefore vary from mild to advanced features of biventricular failure - elevated jugular venous pressure, pulmonary congestion, third heart sound, hepatomegaly and peripheral edema. There may be systolic murmur of mitral regurgitation and tricuspid regurgitation. The presence of irregularly irregular heart rhythm is consistent with atrial fibrillation.

DIAGNOSTIC STUDIES (Table 7)

The chest x-ray may demonstrate cardiomegaly, pulmonary congestion and sometimes pleural effusion.

Laboratory tests Routine tests should include CBC, electrolytes, BUN, creatinine, urinalysis. These tests may not provide the diagnosis but are needed to appropriately manage a patient. Acute and convalescent serum viral titers may be considered when the diagnosis of viral etiology is entertained but the results are generally not useful in making a therapeutic decision. Individual patients should be considered for HIV testing, SLE, ANA tests etc. guided by clinical examination and other routine tests.

Electrocardiogram is also abnormal but not specific for dilated cardiomyopathy. It may reveal atrial fibrillation, left ventricular hypertrophy or BBB (usually LBBB). A 24 hour ambulatory recording of heart rhythm ("Holter") may show frequent ventricular ectopy including nonsustained ventricular tachycardia (NSVT).

Echocardiogram This is the most useful test and characteristically demonstrates dilated cardiac chambers with global hypokinesis and a low ejection fraction. It may also reveal the presence of mitral and tricuspid regurgitation and rarely, intracardiac clot.

Cardiac catheterization is performed only in patients suspected to have a specific pathology - coronary artery disease or valve disease.

Transvenous Myocardial Biopsy. This is performed rarely and in selected cases for diagnostic purpose and to follow the course of patients receiving anthracyclines and to detect early changes of rejection following cardiac transplantation. Other conditions where this procedure may be helpful include infiltrative diseases such as hemochromatosis, amyloidosis, sarcoidosis, etc.

TREATMENT (Table 8)

The treatment of a patient with dilated cardiomyopathy is directed at managing congestive heart failure. This includes general measures - weight control, cessation of smoking, restriction of salt in diet, moderation or cessation of alcohol intake and management of coexisting conditions e.g. coronary artery disease, hypertension, etc.

Specific therapy consists of diuretics to control pulmonary congestion and peripheral edema. Angiotensin converting enzyme inhibitors are the mainstay of therapy and have been shown to prolong survival, besides improving symptoms and quality of life. ACE inhibitors are contraindicated in pregnancy (because of adverse effects on fetus) and in patients with hyperkalemia or advanced renal failure. Digoxin provides additional symptom relief especially in patients with concomitant atrial fibrillation. However, no survival benefit has been noted with digoxin therapy. Beta blockers are added to conventional treatment in patients whose heart failure has been stabilized. Beta blockers have shown to provide additional symptom relief and survival benefit. Those with atrial fibrillation should receive chronic anticoagulation to prevent thromboembolic complications. Selected patients with refractory heart failure are referred for cardiac transplantation.

PROGNOSIS

Despite progress in the management of heart failure, patients with dilated cardiomyopathy generally have a poor prognosis unless an incriminating factor is identified and discontinued e.g. alcohol. Patients die of progressive heart failure but sudden death from ventricular fibrillation is common. Implantable automatic defibrillators prevent recurrent cardiac arrest due to ventricular tachycardia/ventricular fibrillation. Antiarrhythmic agents are generally avoided due to the increased risk of proarrhythmia.


TABLE 1

CLASSIFICATION
 

WORLD HEALTH ORGANIZATION (WHO)
 

1. DILATED - DILATED CARDIAC CHAMBERS;

MILD HYPERTROPHY
 

2. HYPERTROPHIC - NORMAL SIZED CHAMBERS;

SEVERE HYPERTROPHY
 

3. RESTRICTIVE - NORMAL SIZED CHAMBERS;

NORMAL/ MILD HYPERTROPHY
 
 


TABLE 2

MAJOR FEATURES
 
 

  Dilated CM Hypertrophic CM Restrictive CM
CHAMBERS: DILATED NORMAL NORMAL
WALL HYPERTROPHY: MILD SEVERE MILD
SYSTOLIC FUNCTION: DIMINISHED NORMAL/HYPERDYNAMIC NORMAL
DIASTOLIC FUNCTION:
(COMPLIANCE)
NORMAL * ¯COMPLIANCE ¯ COMPLIANCE
EJECTION FRACTION: REDUCED NORMAL/HIGH NORMAL

        * Note that in Dilated CM, compliance is initially normal, and then becomes reduced.
 
 
 


TABLE 3

DILATED CARDIOMYOPATHY

ETIOLOGY

IDIOPATHIC

INFECTION - VIRAL (COX B), RICKETTSIAL, PARASITIC

PERIPARTUM

CONNECTIVE TISSUE DISEASE (SLE)

TOXIC - ALCOHOL, ADRIAMYCIN, COCAINE

NEUROMUSCULAR

METABOLIC -- THYROID DISORDERS, NUTRITIONAL DEFICIENCIES, PROLONGED TACHYCARDIA

ISCHEMIC -- MULTIPLE MYOCARDIAL INFARCTS

FAMILIAL
 
 


TABLE 4A

PATHOPHYSIOLOGY

DILATED CARDIOMYOPATHY

DILATED CARDIAC CHAMBERS

MILD HYPERTROPHY

IMPAIRED SYSTOLIC FUNCTION

CARDIAC OUTPUT: EARLY - NORMAL (Frank-Starling) (increased heart rate)

LATE - DECREASED

COMPLIANCE: EARLY = NORMAL;  LATE = DECREASED

MITRAL AND TRICUSPID REGURGITATION (DUE TO VENTRICULAR DILATION)

ATRIAL FIBRILLATION; BUNDLE BRANCH BLOCK

INTRACARDIAC THROMBI
 
 
 


TABLE 4B

DILATED CM - PATHOPHYSIOLOGIC BASIS OF CLINICAL FEATURES

 
PATHOPHYSIOLOGY CLINICAL FEATURES
DECREASED  CARDIAC OUTPUT  (¯ EF) FATIGUE
DECREASED  RENAL BLOOD FLOW ­ RAAS (EDEMA, VASOCONSTRICTION)
­ SYMPATHETIC ACTIVITY TACHYCARDIA, VASOCONSTRICTION
DILATED LV, PAPILLARY MUSCLE DYSFUNCTION MITRAL REGURGITATION 
IMPAIRED LV DIASTOLIC COMPLIANCE  ­ LVEDP (DYSPNEA, PULMONARY CONGESTION , S3 )
ELEVATED CENTRAL VENOUS PRESSURE JVD, HEPATOMEGALY, PERIPHERAL EDEMA
DILATED RV TRICUSPID REGURGITATION  (JUGULAR "V" WAVES)
EF = Ejection fraction
­ RAAS = Increased renin-angiogensin/aldosterone system, JVD = Jugular venous distention
LV = Left ventricle; RV = Right ventricle; ­ LVEDP = Elevated left ventricular end diastolic pressure
 
 

TABLE 5
 

DILATED CARDIOMYOPATHY

HISTORY

1. DYSPNEA, FATIGUE, EDEMA

2. NEW ONSET ARRHYTHMIA -- PALPITATIONS, DIZZINESS

3. EMBOLIC EVENT -- CEREBROVASCULAR, PERIPHERAL, OTHER
 
 
 
 
 
 


TABLE 6

DILATED CARDIOMYOPATHY

PHYSICAL EXAMINATION

ELEVATED JUGULAR VENOUS PRESSURE

BIBASILAR RALES

LATERAL DISPLACEMENT OF THE APICAL CARDIAC IMPULSE

S GALLOP

MURMURS OF MITRAL, TRICUSPID INSUFFICIENCY

ENLARGED LIVER

PERIPHERAL EDEMA
 
 
 
 
 


TABLE 7

DILATED CARDIOMYOPATHY

DIAGNOSTIC STUDIES

         1. CHEST X-RAY - ENLARGED HEART, PULMONARY CONGESTION, PLEURAL EFFUSION
2. EKG - ATRIAL FIBRILLATION, BUNDLE BRANCH BLOCK (BBB), VENTRICULAR ARRHYTHMIAS

3. ECHOCARDIOGRAM - DILATED CHAMBERS, DIMINISHED WALL MOTION, THROMBUS, MITRAL AND TRICUSPID REGURGITATION, ETC.

4. RADIONUCLIDE VENTRICULOGRAM - LOW EJECTION FRACTION, POOR SYSTOLIC FUNCTION

5. CARDIAC CATHETERIZATION - DONE IN SELECTED CASES IF THERE IS SUSPICION OF UNDERLYING CAD OR VALVE DISEASE

6. MYOCARDIAL BIOPSY - ALSO PERFORMED IN SELECTED CASES IF IMMUNOSUPPRESSIVE TREATMENT IS BEING ENTERTAINED. IT IS USUALLY HELPFUL IN FOLLOWING THE CONDITION OF PATIENTS AFTER CARDIAC TRANSPLANTATION OR THOSE RECEIVING ANTI-CANCER DRUGS (ANTHRACYCLINES)
 


 
 


TABLE 8

DILATED CARDIOMYOPATHY

TREATMENT

1. GENERAL
A) SALT RESTRICTION; FLUID RESTRICTION;  SMOKING, WEIGHT, ALCOHOL RESTRICTION

B) CORRECT COEXISTING CONDITIONS - CAD, ANEMIA, HYPERTENSION, ETC.
 

 
2. SPECIFIC  
A) DIURETIC

B) ACE INHIBITORS / ANGIOTENSIN RECEPTOR BLOCKERS

C) DIGOXIN

D) ANTICOAGULATION (IF EF IS MARKEDLY REDUCED OR EVIDENCE OF THROMBOEMBOLIC DISEASE)

E) CARDIAC TRANSPLANTATION ( FOR REFRACTORY END-STAGE HEART FAILURE )

F) IMPLANTABLE DEFIBRILLATOR ( FOR VENTRICULAR TACHYCARDIA OR HISTORY OF SUDDEN CARDIAC DEATH)