Harrison's Practice: Dilated Cardiomyopathy

Harrison's Practice

Dilated Cardiomyopathy

Definition

Cardiomyopathy
- A disease affecting the heart muscle that is not the result of congenital, valvular, hypertensive, coronary arterial, or pericardial abnormalities
2 fundamental forms of dilated cardiomyopathy
- Primary myocardial involvement
  - Idiopathic: myocardial disease of unknown cause
  - Familial
    - Caused by mutations of genes encoding sarcomeric, cytoskeletal, contractile, nuclear membrane, and other proteins
- Secondary myocardial involvement
  - Myocardial disease of known cause (e.g., alcoholism) or associated with a disease involving other organ systems
Dilated cardiomyopathy
- Demonstrates symmetrically dilated left and/or right ventricle with impaired systolic contractile function, leading to congestive heart failure, arrhythmias, and emboli

Epidemiology

Incidence/prevalence
- Dilated cardiomyopathy (all types)
  - Cause one-third of congestive heart failure (CHF) cases
  - Prevalence is increasing.
Idiopathic dilated cardiomyopathy
- Incidence
  - 6 cases per 100,000 persons per year
- Prevalence
  - 17.9 cases per 100,000 persons
- Age
  - May occur at any age
  - Most commonly becomes apparent clinically in the third or fourth decades
  - Most commonly a disease of middle-aged men
- Sex
  - More common in men than women
- Race/ethnicity
  - More common among African Americans than white persons
Peripartum cardiomyopathy [1]
- Race/ethnicity
  - Incidence in whites: 1 of 4075 deliveries
  - Incidence in African Americans: 1 of 1421 deliveries
    - 2.9-fold higher incidence compared with whites
    - 7-fold higher incidence compared with Hispanics
  - Incidence in Hispanics: 1 of 9861 deliveries

Risk Factors

Family history
Alcoholism
Advancing age
Pregnancy in patients with previous peripartum cardiomyopathy

Etiology

Primary myocardial involvement

Idiopathic (most common)
- No cause is apparent.
Familial (one-fifth to one-third of cases)
- Most commonly autosomal dominant; can also be autosomal recessive, mitochondrial (especially in children), and X-linked
- Mutations in >20 genes that are transmitted in an autosomal dominant fashion have been described.
  - Most common are mutations in genes encoding sarcomeric proteins, such as α-cardiac actin; β- and α-myosin; heavy chain α-tropomyosin; and troponins T, I, and C.
  - May also exhibit skeletal myopathies, particularly Duchenne’s and Emery-Dreyfuss muscular dystrophy.
  - Mutations in the gene encoding the nuclear envelope protein lamin A/C
    - Responsible for the development of dilated cardiomyopathy associated with atrioventricular (AV) conduction disorder and other electrophysiologic disturbances that may cause sudden cardiac death
- X-linked autosomal recessive disorder
  - Caused by the dystrophin gene
  - Occurs in young males
  - Associated with a rapid downhill course

Secondary myocardial involvement

End result of myocardial damage from a variety of toxic, metabolic, or infectious agents
Possibly mediated by an immunologic mechanism
Infective
- Viral myocarditis
- Bacterial myocarditis
- Fungal myocarditis
- Protozoal myocarditis
- Metazoal myocarditis
- Spirochetal
- Rickettsial
Metabolic
Familial storage disease
- Glycogen storage disease
- Mucopolysaccharidoses
- Hemochromatosis
- Fabry’s disease
Deficiencies
- Electrolytes
- Nutritional
Connective tissue disorders
- Systemic lupus erythematosus
- Polyarteritis nodosa
- Rheumatoid arthritis
- Progressive systemic sclerosis
- Dermatomyositis
Infiltrations and granulomas
- Amyloidosis
- Sarcoidosis
- Cancer
Neuromuscular
- Muscular dystrophy
- Myotonic dystrophy
- Friedreich’s ataxia
Sensitivity and toxic reactions
- Alcohol
  - Large quantities (>90 g/d) of alcohol over many years
- Radiation
- Drugs
  - Anthracycline derivatives: doxorubicin (increased risk with cardiac irradiation, age > 70 years, underlying heart disease, hypertension, treatment with cyclophosphamide)
  - Trastuzumab (Herceptin)
    - Used in the treatment of breast cancer
    - Causes cardiomyopathy in 7% of patients when used as monotherapy and 4 times as frequently when combined with doxorubicin
  - High-dose cyclophosphamide
    - May produce CHF acutely or within 2 weeks of administration
  - Imatinib mesylate (Gleevec)
    - Used in the treatment of chronic myeloid leukemia
    - LV dysfunction has also been reported with administration.
  - Cocaine
Peripartum heart disease
- Last trimester of pregnancy or within 6 months of delivery
- Multiparity
- African-American race
- Age > 30 years
Reversible forms of dilated cardiomyopathy
- Alcoholic cardiomyopathy: consumption of large quantities of alcohol over many years, leading to clinical picture identical to idiopathic dilated cardiomyopathy
- Peripartum cardiomyopathy: cardiac dilatation and CHF of unexplained cause developing during the last trimester of pregnancy or within 6 months of delivery

Symptoms & Signs

Symptoms of left- and/or right-sided CHF

See also Chronic Heart Failure.
Develop gradually in most patients
Disease process may take months or years to become symptomatic.
Common symptoms may include:
- Dyspnea with exertion (early) or at rest (late)
- Orthopnea
  - Dyspnea when recumbent; relief with sitting upright or use of several pillows
- Paroxysmal nocturnal dyspnea
  - Attacks of severe shortness of breath and coughing at night; usually awakens patient
  - Coughing and wheezing often persist even with sitting upright.
  - Cardiac asthma: nocturnal dyspnea, wheezing, and cough due to bronchospasm
- Fatigue and weakness
- Abdominal symptoms
  - Anorexia
  - Nausea
  - Abdominal pain and fullness
- Cerebral symptoms
  - Altered mental status due to reduced cerebral perfusion
    - Confusion
    - Difficulty concentrating
    - Impaired memory
    - Headache
    - Insomnia
    - Anxiety
    - Depression
- Sexual dysfunction
- Nocturia

Less common symptoms include:
- Vague chest pain
  - Typical angina pectoris is unusual and suggests concomitant ischemic heart disease.
- Syncope
Patients with alcoholic cardiomyopathy may not show other evidence of alcohol abuse, such as liver disease.

Physical findings

Pulmonary rales, with or without expiratory wheeze
Lower-extremity edema
Hydrothorax (pleural effusion)
Ascites
Congestive hepatomegaly
- Positive abdominojugular reflux
Jugular venous distention
Third and fourth heart sounds: often present but not specific
Elevated diastolic arterial pressure
Findings in late/severe heart failure
- Pulsus alternans
  - Regular rhythm with alternation in strength of peripheral pulses
  - Most common in cardiomyopathy and hypertensive and ischemic heart disease
- Diminished pulse pressure
- Elevated jugular venous pressure
- Third and/or fourth heart sounds
- Murmur of mitral or tricuspid regurgitation
- Jaundice
- Decreased urine output
- Cardiac cachexia

Differential Diagnosis

Must be distinguished from all other causes of heart failure
Diseases that must always be considered are:
- Hypertrophic cardiomyopathy
- Restrictive cardiomyopathy
- Ischemic heart disease
- Valvular heart disease
  - Chronic aortic/mitral regurgitation

Diagnostic Approach

History and physical examination, with particular attention to family history and risk factors
Appropriate laboratory testing and imaging studies
Exclude:
- Hypertension
- Congenital or acquired disease
  - Valvular abnormalities: usually requires echocardiography
  - Coronary abnormalities: usually requires coronary arteriography
  - Pericardial abnormalities (See Chronic Constrictive Pericarditis.)

Laboratory Tests

Brain natriuretic peptide
- Level elevated in heart failure vs lung disease
- Identifies patients at increased risk of sudden death
- Levels >100 pg/mL diagnose heart failure with 90% sensitivity and a lower (~75%) specificity.
Additional laboratory tests may be indicated depending on the clinical presentation and any associated underlying disorders.
- In a patient with an acute presentation, cardiac enzymes will almost always be ordered.

Imaging

Chest radiography
- Moderate to marked cardiac silhouette enlargement
- Often generalized cardiomegaly
- Pulmonary venous hypertension
- Interstitial or alveolar edema
Echocardiography, computed tomographic imaging (CTI), and cardiac magnetic resonance imaging (CMRI)
- Left ventricular dilatation; globally impaired contraction
- Normal, minimally thickened, or thinned walls
- Systolic dysfunction (reduced ejection fraction)
- Cardiac CTI may distinguish between dilated cardiomyopathy and proximal coronary artery disease (reducing the need for invasive procedures).

Diagnostic Procedures

Electrocardiography may show:
- Diffuse, nonspecific ST and T-wave abnormalities
- Sinus tachycardia
- Atrial fibrillation
- Ventricular arrhythmias
- Left atrial abnormality
- Intraventricular and/or AV conduction defects
- Low voltage
Cardiac catheterization and coronary angiography
- To exclude ischemic heart disease
- In cardiomyopathy, usually reveals:
  - Left ventricular dilatation and dysfunction
  - Mitral regurgitation
  - Elevated left- and often right-sided filling pressures
  - Diminished cardiac output
- Cardiac CTI may distinguish between dilated cardiomyopathy and proximal coronary artery disease (reducing the need for invasive procedures).
Transvenous endomyocardial biopsy
- Usually not helpful in idiopathic or familial dilated cardiomyopathy
- Used to diagnose secondary cardiomyopathies (e.g., amyloidosis, acute myocarditis)

Treatment Approach

Provide standard therapy for CHF in most cases.
Treat underlying disease when present.

Specific Treatments

Idiopathic dilated cardiomyopathy

Standard therapy of CHF (See Chronic Heart Failure for details.)
- Salt restriction
- Angiotensin-converting enzyme (ACE) inhibitor
  - Angiotensin receptor blocker if the patient is ACE intolerant
- Diuretics
- Digoxin
- Add β blocker in most patients.
- Add spironolactone in recent or current advanced heart failure.
Chronic anticoagulation
- Warfarin
- Recommended for very low ejection fraction (< 25%), if no contraindications
Antiarrhythmic drugs
- Avoid except for symptomatic or sustained arrhythmias.
Implantable cardioverter defibrillator (ICD)
- Indications: ejection fraction < 30%; symptomatic ventricular arrhythmia
Biventricular pacing (resynchronization therapy)
- Indications: persistently symptomatic patients despite optimum pharmacologic therapy with widened (≥130 ms) QRS complex (e.g., right or left bundle-branch block)
- Outcome: improves symptoms, reduces hospitalizations, may reduce mortality
Cardiac transplantation
- Indications: patients refractory to medical therapy
Avoidance of the following substances
- Alcohol
- Calcium-channel blockers
- NSAIDs

Alcoholic cardiomyopathy

Ceasing alcohol consumption before severe heart failure develops may halt progression or reverse the course.

Peripartum cardiomyopathy

Treatment as for idiopathic dilated cardiomyopathy (including implantation of an ICD or cardiac transplantation if the criteria for these therapies are satisfied).
Encourage patient to avoid further pregnancies.

Cardiomyopathy related to neuromuscular disease

Permanent pacemaker in appropriate patients

Drug-related cardiomyopathy

Chemotherapeutic agents
- Modify chemotherapeutic dose schedule to give drug more slowly.
- Selective addition of potentially cardioprotective agents (e.g., an iron-chelator: dexrazoxane)
- Aggressive management with ACE inhibitors and diuretics
Cocaine-induced cardiotoxicities
- Nitrates, calcium-channel blockers, and benzodiazepines
- Avoid β-adrenergic blockers.

Monitoring

Bedside hemodynamic monitoring in acutely decompensated patients
Monitor for progression and complications.
Monitor response to therapy.

Complications

CHF
Ventricular thrombus
Systemic embolization from ventricular thrombus
Syncope
Arrhythmias
Sudden death

Prognosis

Idiopathic dilated cardiomyopathy
- Progressive downhill course
- Most patients (particularly those > 55 years) die within 4 years of development of symptoms (heart failure).
- Death or sudden death occurs from:
  - CHF
  - Ventricular tachyarrhythmia or bradyarrhythmia
- Progressive heart failure and death are more likely in African Americans than in white persons.
- Spontaneous improvement or stabilization occurs in ~ 25% of patients.

Alcoholic cardiomyopathy
- Poor prognosis, particularly with continued alcohol intake
- < 25% survive 3 years.
Peripartum cardiomyopathy
- Mortality rate ≈ 10%
  - A study[1] revealed the freedom from all-cause death was 96.7% at a mean follow-up of 4.7 years.
    - Current mortality associated with peripartum cardiomyopathy may be less than reported in older series, perhaps because of the high utilization of modern heart failure therapy.
- Prognosis depends on heart size after first episode of CHF.
  - If returns to normal: Subsequent pregnancies may sometimes be tolerated but with increased risk of recurrent heart failure, and should be avoided.
  - If remains enlarged, and/or the LV EF remains depressed after 6 months: Prognosis is poor.
    - Frequently, myocardial damage occurs with further pregnancies, ultimately leading to refractory CHF and death; further pregnancies must be avoided.
Cardiomyopathy related to neuromuscular disease
- Rapidly progressive CHF despite extended periods of apparent circulatory stability
- Syncope and sudden death are possible.
Drug-related cardiomyopathy
- Prognosis is related to drug dose plus presence or absence of concomitant conditions.
- Heart failure and sudden death are possible.
Connective tissue disease and cardiomyopathy
- According to a study:[2]
  - Diagnosis of cardiomyopathy and either undifferentiated connective tissue disease or systemic sclerosis appears to be a poor prognostic indicator compared with the diagnosis of idiopathic dilated cardiomyopathy.
  - Diagnosis of cardiomyopathy and systemic lupus erythematosus has a similar prognosis to that of idiopathic dilated cardiomyopathy.

Prevention

Peripartum cardiomyopathy
- After recovery, the patient should be encouraged to avoid future pregnancies, particularly if cardiomegaly persists.
Alcoholic cardiomyopathy
- Ceasing alcohol use before severe heart failure may halt progression or even reverse the course of disease.
Moderate alcohol consumption (20–30 g/d) appears to be cardioprotective.
- Raises high-density lipoprotein cholesterol
- Associated with a reduced incidence of ischemic heart disease, ischemic stroke, and metabolic syndrome

ICD-9-CM

425.4 Other primary cardiomyopathies