Basics
Description
- Dilated cardiomyopathy (DCM) is the most common type of cardiomyopathy.
- It is due to a number of potential etiologies but is most often idiopathic.
- DCM is characterized by LV and/or RV enlargement with reduced systolic function, and progressive heart failure with increased risk for sudden cardiac death.
Epidemiology
- DCM accounts for ~60% of all cardiomyopathies.
- Incidence of DCM is 5-8 cases per 100,000 persons per year in U.S. and Europe.
- Prevalence of DCM is ~40 cases per 100,000 persons in U.S.; prevalence is increasing, likely due to more thorough testing.
- >1/2 of DCM cases in the Western world are idiopathic, with an estimated 30-50% of these cases being genetic.
- Male > Female
- Most common presentation is in the 4th-5th decades of life; but DCM can occur in people of all ages.
Risk Factors
- Family history of dilated cardiomyopathy
- Alcohol or cocaine abuse
- Viral infections (see list under Etiology)
- For peripartum DCM: Multiparity; advanced maternal age; African American
Genetics
- Among idiopathic DCM cases, it is estimated that 30-50% are actually genetic in etiology.
- Mutations in >20 genes are known to cause DCM: Cardiac actin (ACTC); α-tropomyosin (TPM1); β-myosin heavy chain (MYH7); troponins T, I, & C (TNNT2, TNNI3, TNNC1); myosin-binding protein-C (MYBPC-3); titin (TTN); telethonin (TCAP); desmin (DES); dystrophin (DMD); metavinculin (VCL); δ-sarcoglycan (SGCD); cardiac muscle LIM protein (CLP); α-actinin (ACTN2); cypher/ZASP; Lamin A/C (LMNA); thymopoietin (LAP2); cardiac sodium channel (SCN5A); ATP-binding cassette transporter (ABCC9); phospholamban; tafazzins (G4.5).
- Most mutations have an autosomal dominant mode of inheritance with incomplete penetrance due to modifier genes and environmental factors. Autosomal recessive and X-linked inheritance are less common.
Pathophysiology
- An index event or process (depending on underlying etiology) damages the myocardium and prevents normal contraction.
- Neurohormonal pathways, including the sympathetic nervous system and the renin-angiotensin- aldosterone system initially compensate to maintain cardiac output and effective arterial blood volume.
- Over time, excessive neurohumoral activity leads to ventricular remodeling, including cardiomyocyte hypertrophy, myocardial fibrosis, and myocyte dropout. Other factors involved include oxidative stress, inflammation (tumor necrosis factor and interleukin-1), calcium-regulatory proteins and nitric oxide dysfunction.
- Symptoms are often not apparent until after LV remodeling has taken place. Reverse remodeling can occur with treatment.
Etiology
- Idiopathic:
- >50% of DCM cases are idiopathic
- Estimated 30-50% of idiopathic DCM cases are genetic
- Myocarditis:
- Viral: Adenovirus and enterovirus (commonly coxsackie virus B3) are the predominant viral etiologies of DCM in the U.S.
- Other infections: Trypanosoma cruzi (Chagas disease); Borrelia burgdorferi (Lyme disease)
- Hypersensitivity: Sulfonamides, cephalosporins, penicillins, tricyclic antidepressants
- Autoimmune: Giant cell myocarditis, systemic lupus erythematosus, Churg-Strauss, inflammatory bowel disease
- Toxin: Alcohol is the most common cause of nonischemic DCM in the Western world, accounting for 21-36% of cases:
- Cocaine, amphetamines, cobalt, lead, mercury
- Ischemic heart disease: A common cause of DCM in U.S.
- Peripartum cardiomyopathy: ~1/4,000 births; typically occurs in the 3rd trimester or within 6 mo postpartum.
- Neuromuscular disorders: Duchenne muscular dystrophy; myotonic dystrophy
- Endocrinological disorders: Thyroid disease; DM; Cushing disease; growth hormone excess or deficiency; pheochromocytoma
- Medications: Chemotherapies (anthracyclines, cyclophosphamide, doxorubicin, trastuzumab), antiretrovirals (zidovudine, didanosine, zalcitabine), chloroquine, phenothiazines, clozapine
- Nutritional deficiencies: Carnitine, selenium, thiamine
- Miscellaneous: Tachycardia, valvular heart disease, radiation, uremia, end-stage renal disease on hemodialysis, obstructive sleep apnea
Associated Conditions
- Venous thromboembolic disease is common due to stasis, endothelial dysfunction, and chronic elevation of proinflammatory cytokines.
- Anemia is common, present in >50% of patients admitted with heart failure, due to hemodilution, as well as chronic renal dysfunction.
- Atrial and ventricular arrhythmias, and sudden cardiac death
Diagnosis
History
- A thorough review of systems is essential to determine the underlying etiology. Inquire about heart disease and anginal symptoms, infections and viral symptoms, medications, previous cancer treatment, drug and alcohol use, travel, occupation-related toxin exposure.
- Family history of heart disease and sudden death should be elicited, as well as planning for potential screening of 1st-degree relatives.
- Symptoms of heart failure: Dyspnea, exercise intolerance, orthopnea, PND, cough or wheezing, peripheral edema, anorexia, early satiety, abdominal pain and fullness, and fatigue
Physical Exam
- A complete exam by organ system may give clues regarding the etiology of the DCM.
- Signs of heart failure or cardiomegaly: Tachycardia, tachypnea, elevated JVP, pulmonary rales, 3rd heart sound (S3), 4th heart sound (S4), diminished or laterally displaced PMI, mitral and/or tricuspid regurgitation, hepatomegaly, ascites, peripheral edema, pleural effusion
Tests
Lab
- For all cases, standard labs should include: CBC with differential, comprehensive metabolic panel, hepatic function panel, thyroid stimulating hormone, BNP or pro-BNP, troponin, lipid panel
- Additional lab workup depends on suspected etiology of DCM.
- EKG
Imaging
- CXR may reveal cardiomegaly and/or pulmonary vascular congestion.
- Echo: The cornerstone of diagnosis and monitoring of patients with DCM. 2-dimensional echo reveals LV and/or RV dilatation with impaired cardiac function. Later stages of disease may reveal restrictive filling, atrioventricular valvular regurgitation, atrial dilation, and intracardiac thrombi.
- Cardiac MRI:
- Provides precise assessment of cardiac structure and function. Delayed enhancement imaging revealing diffuse vs. focal enhancement may be helpful to determine both etiology and potential diagnostic yield of endomyocardial biopsy.
Surgery
- Endomyocardial biopsy: Not commonly indicated as part of work up. Diagnostic yield for new cardiomyopathy of unknown etiology is ~15%. Biopsy should be reserved for certain scenarios, including: New-onset heart failure <2 wk duration with hemodynamic compromise; new-onset DCM of 2 wk-3 mo duration with ventricular arrhythmia, 2nd- or 3rd-degree AV block, or failure to respond to therapy within 1-2 wk, DCM with suspected allergic reaction and/or eosinophilia, suspected anthracycline toxicity.
- Coronary angiography: Indicated in patients with suspected coronary artery disease
- Genetic testing:
- Not recommended as part of standard workup for DCM
- One exception is the lamin A/C gene: It is the most frequent genetic defect known to cause DCM.
- Screening family members: 30% of patients have a family member with either overt DCM or echo evidence of LV dysfunction or enlargement. In families with ≥2 patients with DCM (or sudden cardiac death <30), screening of 1st- and 2nd-degree family members with history, physical exam, EKG, and echo is warranted. If there are signs of lamin A/C mutation, then genetic testing should be performed.
Pathological Findings
- Gross: 4-chamber enlargement, and often increased ventricular wall thickness. Intracardiac thrombi may be present.
- Histology: Myocyte hypertrophy and interstitial fibrosis.
Differential Diagnosis
Cardiac amyloidosis, sarcoidosis, hemochromatosis, and hypertensive cardiomyopathies typically present as restrictive cardiomyopathy, but may present as DCM. �
Treatment
Medication
- Mainstays of medical management of compensated DCM include neurohormonal antagonists to prevent further remodeling and promote reverse remodeling, and diuretics to manage excessive salt and water retention.
- ACE inhibitors and/or ARBs are standard-of-care; both are contraindicated in pregnancy.
- β-Adrenergic blockers are standard-of-care; titrate judiciously.
- Hydralazine and nitrates may be used in addition to, or as alternative to ACE inhibitors, especially in African American patients.
- Aldosterone antagonists
- Thiazide and loop diuretics are typically necessary.
- Digoxin may be used, especially if atrial fibrillation is present.
- Amiodarone may be useful for rhythm control in the setting of atrial fibrillation or ventricular arrhythmias, but has not been shown to provide mortality benefit.
- Warfarin for atrial fibrillation or treatment of thrombi; contraindicated in pregnancy.
Additional Treatment
Issues for Referral
Patients with end-stage heart failure or anticipated end-stage heart failure should be referred to a cardiac transplantation center. �
Additional Therapies
Stem cells are under investigation. �
Surgery
- Implantable cardioverter-defibrillator is recommended for any of the following:
- Previous ventricular fibrillation (VF) or hemodynamically unstable ventricular tachycardia (VT)
- Spontaneous sustained VT
- Unexplained syncope with inducible VT or VF upon electrophysiological testing
- Ischemic DCM with LVEF ≤35%, >40 days post MI, and NYHA Class II-III heart failure
- Ischemic cardiomyopathy with LVEF ≤30%, >40 days post MI, and NYHA class I.
- Ischemic cardiomyopathy with LVEF ≤40%, nonsustained VT, and inducible VF or sustained VT upon electrophysiological testing
- Nonischemic DCM with LVEF ≤35% and NYHA class II-III heart failure
- Permanent pacemaker: Indicated for treatment of sinus node dysfunction or high-grade AV node block.
- Cardiac resynchronization therapy is indicated in patients with LVEF ≤35%, QRS ≥120 msec, and NYHA Class III-IV heart failure symptoms despite optimal medical therapy.
- Coronary revascularization for ischemic cardiomyopathy
- Cardiac transplantation and ventricular assist devices are used in severely ill patients.
In-Patient Considerations
Admission Criteria
Admit patients with acute decompensated heart failure requiring IV diuresis and/or inotropic support. �
Discharge Criteria
- Resolution of heart failure symptoms
- Stable weight
- Patient and provider should have a plan to prevent inciting events that cause acute decompensation
Ongoing Care
Follow-Up Recommendations
Patient Monitoring
Cardiopulmonary exercise testing: A precise assessment of functional status. A peak oxygen consumption of ≤10 mL/kg/min (≤14 mL/kg/min, in specific cases) is an indicator of potential benefit from cardiac transplantation. �
Diet
Sodium-restricted �
Prognosis
- Median survival after diagnosis is 5 yr, but prognosis varies widely depending on etiology. Common causes of death include progressive heart failure, arrhythmias, and thromboembolic events.
- Etiologies that are typically reversible include alcohol, tachycardia, viral, and peripartum cardiomyopathies. Peripartum cardiomyopathies show significant improvement within 6 mo in ~50% of all women with this disorder.
- Idiopathic DCM is the 2nd most common cause of sudden cardiac death, representing 10% of cases. About 30% of deaths in idiopathic DCM are due to sudden cardiac death. High-risk features include nonsustained VT, syncope, and advanced heart failure symptoms. ICD for primary prevention provides mortality benefit.
- Idiopathic DCM is the most common reason for cardiac transplantation.
Additional Reading
1
Cooper �LT, Baughman �KL. The role of endomyocardial biopsy in the management of cardiovascular disease: A scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. Circulation. 2007;116(19):2216-2233. �[View Abstract] 2
Hare �JM.
The dilated, restrictive, and infiltrative cardiomyopathies. In: Libby �PBraunwald's heart disease: A textbook of cardiovascular medicine, 8th ed.Philadelphia: Saunders, 2008;1739-1762. 3
Karkkainen �S, Peuhkurinen �K.
Genetics of dilated cardiomyopathy. Ann Med. 2007;39(2):91-107. �[View Abstract] 4
Luk �A, Ahn �E. Dilated cardiomyopathy: A review. J Clin Pathol. 2009;62(3):219-225. �[View Abstract]
Codes
ICD9
- 425.4 Other primary cardiomyopathies
- 428.0 Congestive heart failure, unspecified
- 674.50 Peripartum cardiomyopathy, unspecified as to episode of care or not applicable
SNOMED
- 399020009 congestive cardiomyopathy (disorder)
- 195021004 primary dilated cardiomyopathy (disorder)
- 16253001 dilated cardiomyopathy secondary to peripartum heart disease (disorder)
Clinical Pearls
- DCM accounts for ~60% of all cardiomyopathies.
- >1/2 of DCM cases are idiopathic, with an estimated 30-50% of those thought to be genetic in etiology.
- A comprehensive history is key to determination of underlying etiology.
- Genetic testing and endomyocardial biopsy are not typically part of the standard workup.