Basics
Description
Cardiomyopathy (CM) is defined as a disease of the heart muscle, which results in impaired function (systolic, diastolic, or both). It is classified based on structural and functional abnormalities:
- Dilated cardiomyopathy (DCM): The key finding is impairment of ventricular systolic function with cardiac dilation. Predominantly involves the left ventricle (LV) and manifests as congestive heart failure (CHF).
- Hypertrophic cardiomyopathy (HCM): Excessive thickening of the LV that is not secondary to load conditions, such as aortic stenosis or hypertension. Up to 20-25% of patients exhibit LV outflow tract obstruction.
- Restrictive cardiomyopathy (RCM): A myocardial disease in which there is impairment of ventricular diastolic function (or relaxation) from increased stiffness of the ventricle. This results in decreased ventricular filling while systolic function is generally preserved.
- Left ventricular noncompaction (LVNC): A disease where the myocardium of the LV has not completely compacted, resulting in persistence of trabeculations and myocardial dysfunction.
Epidemiology
Incidence
- Overall incidence of CM is 1-2 cases per 100,000 children per year. There is a peak incidence during the 1st year of life and a 2nd peak in adolescence.
- DCM: 0.3-2.6 cases per 100,000 children per year
- HCM: 0.3-0.5 cases per 100,000 children per year
Prevalence
- DCM: 36 cases per 100,000 people
- HCM: ~10-20 cases per 100,000 people
- RCM: Least common form of CM (<5%)
- LVNC: ~9% of CM cases
Risk Factors
Genetics
- DCM: familial DCM ~20% of cases
- Autosomal dominant inheritance remains the most common pattern. Although no specific gene has been identified as the cause of familial DCM, 6 genes have been localized in different family cohorts.
- DCM has also been seen in association with diseases of X-linked inheritance, such as Duchenne and Becker muscular dystrophy and Barth syndrome.
- May also be inherited via mitochondrial DNA, with differing penetrance
- HCM: ~60% of reported cases are thought to be inherited. Traditionally, HCM is inherited in an autosomal dominant pattern with incomplete penetrance.
- RCM: Idiopathic cases may have a familial occurrence and may be associated with a skeletal myopathy. An autosomal dominant form of the disease with variable penetrance has been associated with Noonan syndrome.
- LVNC: familial in 20-30%. May be X-linked, mitochondrial, autosomal recessive, or dominant
Etiology
- DCM: There are many etiologies for DCM. Etiology is identified only ~30% of the time.
- Of known causes, the most common is myocarditis (coxsackievirus B, echovirus, adenovirus). DCM can also occur from toxin exposure (anthracyclines), ischemic coronary artery disease (anomalous left coronary artery from the pulmonary artery, coronary aneurysms), and chronic tachyarrhythmias.
- Can occur as a finding associated with another disease or syndrome. These include X-linked muscular dystrophies, inborn errors of fatty acid oxidation, disorders of mitochondrial oxidative phosphorylation, nutritional deficiencies, and primary and secondary carnitine deficiency.
- It may be familial and genetically inherited.
- DCM is most commonly idiopathic.
- HCM: Etiology is known about 25% of the time. Often genetically inherited. Caused by myocyte hypertrophy with fibrillin disarray.
- RCM: Most commonly idiopathic, although known causes include the following:
- Systemic disease such as lupus erythematosus, sarcoidosis, amyloidosis, infiltrative diseases (Gaucher disease, Hurler syndrome), storage diseases (Fabry disease), carcinoid syndrome, and radiation-induced fibrosis
- Familial forms of RCM
Diagnosis
In the early stages of all 3 forms of CM, the symptoms are nonspecific and can mimic other disease processes. The cardiac examination can be completely normal. Therefore, those patients who raise suspicion for this disease either by family history or clinical presentation should be carefully evaluated.
History
- DCM: Symptoms usually develop slowly, although they may also be of sudden onset:
- Irritability
- Respiratory distress
- Dyspnea with exertion
- Anorexia, abdominal pain, nausea
- Failure to thrive
- Exercise intolerance
- Syncope
- Palpitations
- HCM: Children are often asymptomatic and are first referred for evaluation based on family history or for murmur evaluation. Of those with symptoms, the following may be present:
- Chest pain with exertion
- Dizziness
- Syncope
- Palpitations
- RCM: Symptoms are usually due to systemic and pulmonary congestion from high atrial pressures. They are usually more evident late in the disease:
- Dyspnea with exertion
- Abdominal pain
- Chest pain
- Palpitations
Physical Exam
- Cardiac
- DCM: tachycardia, cardiomegaly, hepatomegaly, S3 or S4 gallop; evidence of CHF and decreased cardiac output
- HCM: can be normal or have systolic murmur owing to mitral regurgitation and/or LV outflow tract obstruction. The presence of outflow tract obstruction produces a systolic ejection murmur of variable intensity related to the degree of obstruction; the murmur increases in intensity with Valsalva and decreases in magnitude with squatting. A parasternal or carotid thrill or S4 gallop may be present.
- RCM: Jugular venous pulse either fails to fall or rises during inspiration (Kussmaul sign): the presence of S3 or S4. Advanced cases may exhibit weak peripheral pulses as evidence of low cardiac output.
- Respiratory (DCM and RCM): tachypnea, rales, wheezing
- Abdominal (DCM and RCM): hepatomegaly, ascites, tenderness to palpation
Diagnostic Tests & Interpretation
Lab
Initial Lab Tests
DCM: In addition to routine inflammatory markers, specific tests should be obtained to establish etiology:
- Metabolic: carnitine level, serum organic acids, and urine organic and amino acids, pyruvate, lactate, thyroid function tests
- Genetic: chromosomal analysis, mutations of the dystrophin gene
- Infectious: enterovirus, coxsackievirus A/B, hepatitis, cytomegalovirus, Epstein-Barr virus, adenovirus, parvovirus, herpes simplex virus, and human immunodeficiency virus
- Brain natriuretic peptide (BNP) is often used to follow heart failure in patients with CM.
Imaging
Echocardiogram
- Allows for assessment of systolic function, ventricular dimensions, outflow tract obstruction, and diastolic filling properties
- DCM: significant dilation of left (and right) ventricle with decreased systolic function
- HCM: gold standard for diagnosis: LV hypertrophy, intraventricular pressure gradient, and systolic anterior motion of the mitral valve
- RCM: disproportionately dilated atria with impaired diastolic filling by Doppler. LV function is normal until late stages.
- LVNC: deep trabeculations and intertrabecular recesses in the LV, ventricular hypertrophy, and systolic dysfunction
Diagnostic Procedures/Other
- Nonspecific tests
- Chest radiograph: cardiomegaly, pulmonary venous congestion, pulmonary edema, and pleural effusions; segmental atelectasis from bronchiole compression
- Electrocardiogram: Supraventricular or ventricular arrhythmia may be seen.
- DCM: sinus tachycardia, nonspecific ST segment, and T-wave changes
- HCM: hypertrophy, deep Q waves
- RCM: atrial enlargement, nonspecific ST and T-wave changes
- LVNC: marked ventricular hypertrophy, T-wave inversion
- Cardiac catheterization
- DCM: rarely used as the primary diagnostic tool; the procedure is used to delineate coronary anatomy and to perform endomyocardial biopsies.
- HCM: determination of the presence or absence of LV outflow tract obstruction, evaluation of diastolic dysfunction, classic spike and dome arterial pulse tracing, Brockenbrough phenomenon (a beat following a premature ventricular contraction exhibits an arterial pulse pressure less than that of a control beat)
- RCM: Atrial pressures are elevated from increased LV and right ventricle (RV) end-diastolic pressures. Ventricular pressures exhibit a rapid and deep early decline at the onset of diastole followed by a rapid rise to a plateau in early diastole (dip and plateau or square root sign).
Differential Diagnosis
- DCM: Presentation may mimic other diseases:
- Abdominal distention, right upper quadrant pain, nausea, and anorexia indicate right heart failure but could be mistaken for hepatic or gallbladder disease.
- Wheezing, tachypnea, and dyspnea on exertion may be diagnosed as asthma.
- Cardiomegaly on chest radiograph may be mistaken for a large pericardial effusion.
- HCM: This disease must be differentiated from LV hypertrophy seen in a well-trained athlete.
- RCM: should be distinguished from constrictive pericarditis because the latter is usually a remediable process. A history of tuberculosis, trauma, or cardiac surgery may suggest constrictive pericarditis.
Treatment
General Measures
- DCM
- At diagnosis, a trial of IV γ-globulin and/or other immunomodulators (prednisone, azathioprine) to treat possible myocarditis, although impact on outcomes is unclear
- Diuretics
- Afterload reduction (enalapril, captopril)
- Inotropic agents (milrinone, dobutamine, digoxin)
- Aldactone (improves New York Heart Association [NYHA] functional class)
- Anticoagulation to avoid embolic complications
- Antiarrhythmics as needed
- β-adrenergic blockers (metoprolol, carvedilol)
- Ventricular assist devices have been used in those with end-stage heart failure either as a bridge to recovery or to transplantation.
- HCM: β-adrenergic blockers remain 1st-line medical therapy. Calcium channel blockers or disopyramide may also be used. Antiarrhythmics may also be part of the medical regimen. There is no evidence that prophylactic medical treatment will reduce the risk of sudden death.
- If medical therapy is not effective, other options may include septal myectomy (for severe outflow obstruction) and atrioventricular sequential pacing.
- The placement of an implantable cardioverter-defibrillator (ICD) may be indicated.
- RCM: The mainstay of medical therapy is symptomatic treatment.
- Diuretics can be used with caution to treat venous congestion without reducing the ventricular filling pressure.
- Antiarrhythmics are used to treat the high incidence of atrial arrhythmias.
- ICDs have also been used to treat life-threatening ventricular arrhythmias.
- Anticoagulation is used owing to the high risk of thrombus formation and embolic complications from hemostasis in the dilated atrium.
- Due to natural history of disease, most patients eventually require a cardiac transplant.
- Patients with cardiomyopathies are generally restricted from strenuous exercise due to increased risk of sudden cardiac death.
Surgery/Other Procedures
- DCM or RCM: heart or heart-lung (if the pulmonary vascular resistance is elevated) transplantation; transplantation may be necessary if all therapeutic endeavors prove to be futile.
- HCM: septal myectomy if indicated
Inpatient Considerations
Initial Stabilization
Patients with DCM may present critically ill, requiring intubation and inotropic support.
Ongoing Care
Prognosis
- DCM: The rate of death or transplant is ~30% at 1-year and 40% at 5-year follow-up. Age (<1 month and >6 years), ventricular function, and symptoms of CHF at diagnosis are risk factors for a worse outcome. Biopsy-proven myocarditis is associated with improved outcome.
- HCM: Overall incidence of sudden death is 4-6% in children and adolescents and as low as 1% in adults. Between the ages of 12 and 35 years and in young athletes, HCM is the most common cause of sudden death. Obstruction may slowly develop or progress. Heart failure symptoms usually do not occur until adulthood. Survival is poorer (82%) for those diagnosed at <1 year of age.
- RCM: The reported median survival in RCM is 1.4 years in children with <20% freedom from death or transplant at 5 years.
- LVNC: 5-year survival free of death or transplantation is 75%.
Complications
- CHF can occur in all forms of CM.
- Arrhythmias may be seen and are frequently ventricular in origin.
- Thrombus formation can be seen owing to the stasis of blood in dilated cardiac chambers and the hypocontractile ventricle. Therefore, systemic or pulmonary emboli are possible.
Additional Reading
- Alexander PM, Daubeney PE, Nugent AW. Long-term outcomes of dilated cardiomyopathy diagnosed during childhood. Circulation. 2013;128(18):2039-2046. [View Abstract]
- Alvarez JA, Orav J, Wilkinson JD, et al. Competing risks for death and cardiac transplantation in children with dilated cardiomyopathy. Circ. 2011;124(7):814-823. [View Abstract]
- Ammash NM, Seward JB, Bailey KR, et al. Clinical profile and outcome of idiopathic restrictive cardiomyopathy. Circ. 2000;101(21):2490-2496. [View Abstract]
- Silva JN, Canter CE. Current management of pediatric dilated cardiomyopathy. Curr Opin Cardiol. 2010;25(2):80-87. [View Abstract]
- Towbin JA. Hypertrophic cardiomyopathy. PACE. 2009;32(Suppl 2):S23-S31. [View Abstract]
- Towbin JA, Lowe AM, Colan SD, et al. Incidence, causes, and outcomes of dilated cardiomyopathy in children. JAMA. 2006;296(15):1867-1876. [View Abstract]
- Wilkinson JD, Landy DC, Colan SD, et al. The pediatric cardiomyopathy registry and heart failure: key results from the first 15 years. Heart Failure Clin. 2010;6(4):401-413. [View Abstract]
Codes
ICD09
- 425.4 Other primary cardiomyopathies
- 425.11 Hypertrophic obstructive cardiomyopathy
- 425.9 Secondary cardiomyopathy, unspecified
- 425.18 Other hypertrophic cardiomyopathy
- 425.8 Cardiomyopathy in other diseases classified elsewhere
ICD10
- I42.9 Cardiomyopathy, unspecified
- I42.0 Dilated cardiomyopathy
- I42.5 Other restrictive cardiomyopathy
- I42.8 Other cardiomyopathies
SNOMED
- 85898001 Cardiomyopathy (disorder)
- 399020009 Congestive cardiomyopathy (disorder)
- 89461002 Primary cardiomyopathy
- 90828009 Primary restrictive cardiomyopathy (disorder)
FAQ
- Q: Should family members be evaluated once CM is diagnosed in a 1st-degree relative?
- A: Yes. In some forms of CM, there is a strong genetic component and family members should be evaluated. If the CM is known to be acquired, evaluation of relatives is not required.
- Q: Does the CM of infants of diabetic mothers carry the same clinical course and outcome as that of patients with HCM?
- A: No. The pathophysiology is initially similar in that asymmetric hypertrophy of the ventricular septum is often seen with or without LV outflow obstruction. However, the clinical course of CM in these infants is usually benign and resolves within the first 6 months of life.
- Q: What are the differentiating features of HCM and the benign physiologic hypertrophy of an athlete's heart?
- A: Several criteria are used to make this distinction. For example, a familial history of HCM raises the suspicion of this entity. Studies have suggested specific echocardiographic LV dimensions to differentiate benign hypertrophy and HCM (i.e., a wall thickness of ≥15 mm or LV cavity dimension <45 mm are more consistent with HCM). Also, evidence of abnormal mitral valve inflow is suggestive of HCM.