AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Background

Cardiomyopathies are an important and heterogeneous group of diseases. The concept of heart muscle disease has a notable and evolving history. In the mid 1850s, chronic myocarditis was the only recognized cause of heart muscle disease. In 1900, the designation of primary myocardial disease was introduced, and it was not until 1957 that the term "cardiomyopathy" was used for the first time. Over the subsequent years, a number of definitions for cardiomyopathies have been advanced in concert with an increasing understanding of these diseases.

Cardiomyopathies have traditionally been divided into 3 types (ie, dilated, hypertrophic, restrictive); however, the classification of cardiomyopathies continues to evolve based on the rapid evolution of molecular genetics as well as the introduction of recently described diseases. For the purposes of this article, dilated cardiomyopathy refers to the subset of cardiomyopathies characterized by dilation and contractile dysfunction of the left and right ventricles that is not due to hypertension or ischemic heart disease. 

Pathophysiology

A diverse range of conditions that promote cardiomyocyte injury or loss may cause dilated cardiomyopathy. Dilated cardiomyopathy is characterized by ventricular chamber enlargement and systolic dysfunction with normal left ventricle (LV) wall thickness. Ventricular enlargement and dysfunction generally leads to progressive heart failure with further decline in LV contractile function. Sequelae include ventricular and supraventricular arrhythmias, conduction system abnormalities, thromboembolism, and sudden or heart failure–related death.

Compensatory mechanisms associated with low cardiac output induce reflex upregulation of sympathetic tone and the renin-angiotensin axis, causing increased release of vasopressin, aldosterone, and atrial natriuretic peptide. Stimulation of these hormonal tracts results in volume expansion, which induces vasoconstriction. Vasoconstriction increases afterload that, in turn, decreases stroke volume. As cardiac output depends on stroke volume and heart rate, vasoconstriction ultimately can contribute to decreased cardiac output. Treatment of dilated cardiomyopathy is directed at interrupting this negative cycle.

Frequency

United States

Dilated cardiomyopathy is a common and largely irreversible form of heart muscle disease with an estimated prevalence of 1:2500. It is the third most common cause of heart failure and the most frequent cause of heart transplantation.

In total, an estimated 5 million Americans experience heart failure (including those with left ventricular failure), with more than 500,000 new cases diagnosed annually.

Mortality/Morbidity

From 1993-2003 deaths from heart failure increased by 20.5%. The 2003 death rate was 19.7 per 100,000 overall.¹ Demographic distribution of the death rate was as follows:

• White males - 20.5 per 100,000
• White females - 18.4 per 100,000
• Black males - 23.4 per 100,000
• Black females - 20.4 per 100,000

Hyponatremia at the time of presentation was found to be a marker of increased stimulation of the renin-angiotensin axis and of worsening of the disease course and prognosis.

Age

Dilated cardiomyopathy may manifest clinically at a wide range of ages (most commonly in the third or fourth decade but also in young children).

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

History

• Determine the severity of disease, possible causes, and symptomatology when taking the history of a patient with suspected cardiomyopathy. Symptoms are a good indicator of the severity of the disease and may include the following:
• • Fatigue
  • Dyspnea on exertion, shortness of breath
  • Orthopnea, paroxysmal nocturnal dyspnea
  • Increasing edema, weight, or abdominal girth 
• Note other important patient information, including the following:
• • Age
  • Sex
  • Race
  • Medical history, especially the following:
  • • Hypertension
    • Angina
    • Coronary artery disease
    • Anemia
    • Thyroid dysfunction
    • Breast cancer
    • Prior history of heart failure or myocardial injury
  • Medications (especially new medications or lack of compliance with current medications)
  • Social history (eg, tobacco, alcohol, illicit drug use)
  • Family history of cardiomyopathy or sudden cardiac death

Physical

• On physical examination, look for signs of heart failure and volume overload. Assess vital signs with specific attention to the following:
• • Tachypnea
  • Tachycardia
  • Hypertension
• Other pertinent findings include the following:
• • Signs of hypoxia
  • Jugular venous distension (JVD)
  • Pulmonary edema (crackles and/or wheezes)
  • S₃ gallop
  • Enlarged liver or presence of hepatojugular reflex
  • Peripheral edema

Causes

About 20-30% of dilated cardiomyopathy cases have been reported as familial, although with incomplete and age-dependent penetrance, and linked to a diverse group of more than 20 loci and genes. Although genetically heterogeneous, the predominant mode of inheritance for dilated cardiomyopathy is autosomal dominant, with X-linked, autosomal recessive, and mitochondrial inheritance less frequent. Several of the mutant genes linked to autosomal dominant dilated cardiomyopathy encode the same contractile sarcomeric proteins that are responsible for hypertrophic cardiomyopathy, including α-cardiac actin; α-tropomyosin; cardiac troponin T, I, and C; and β- and α-myosin heavy chain. Research to determine further disease loci is ongoing.

The dilated cardiomyopathy phenotype with sporadic occurrence may derive from a particularly broad range of primary (and secondary) causes, including the following:

• Chronic excessive alcohol consumption
• Other drugs
• • Heavy metals
  • Emetine
  • Anthracyclines (daunorubicin and doxorubicin)
  • Cocaine
  • Methamphetamine
  • Cobalt
• Infections
• • Viral endocarditis/myocarditis (coxsackievirus, adenovirus, parvovirus, human immunodeficiency virus [HIV])
  • Parasites
  • Protozoa
  • Chagas disease (most common cause in parts of South America)
• High-output states
• • Anemia
  • Thyrotoxicosis
  • Pregnancy
• Collagen vascular disease
• Glycogen storage disease, type IV also known as Andersen disease is associated with DCM. 
• Thiamine deficiency and zinc deficiency
• Hypophosphatemia
• Amyloidosis
• Neuromuscular disorders (Duchenne/Becker and Emery-Dreifuss muscular dystrophies)
• Pheochromocytoma

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Other Problems to be Considered

Drug toxicity (eg, emetine, doxorubicin, cobalt)
Glycogen storage disease
Thiamine deficiency
Zinc deficiency
Amyloidosis
Collagen vascular disorders
Neuromuscular disorders
Genetic disorder

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Lab Studies

• Cardiac biomarkers: These can help differentiate ischemic heart disease from dilated cardiomyopathy. Acute coronary syndrome should be considered as a potential etiology for acute decompensation in a patient with a history of heart failure. Further, while the precise role of cardiac biomarkers is still being defined, there is evidence that patients who present with elevated markers experience more severe failure and higher mortality.^{3, 4}
• B-type natriuretic peptide (BNP): This study helps monitor the presence and severity of fluid overload. Changes in BNP level can reflect response to treatment. A low level of B-type natriuretic peptide is helpful in ruling out the condition. However, an elevated B-type natriuretic peptide may be difficult to interpret in patients with stable, compensated heart failure, because they often have chronically elevated levels of this peptide. In a recent study, a low serum BNP proved to be the most useful test (serum B-type natriuretic peptide <100 pg/mL; negative LR = 0.11; 95% CI, 0.07-0.16).⁵
• Sequential multiple analysis (SMA)-20
• Thyroid function tests: Thyrotoxicosis is associated with a high-output state that may predispose to dilated cardiomyopathy. Results of this panel are not usually available to assist in decision making in the ED but may be sent for convenience.
• Complete blood count (CBC): Anemia can also be associated with a high-output state.
• Urine pregnancy test: Pregnancy is also associated with a high-output state.
• Urine toxicology screen: This study is used to detect drugs associated with risk for dilated cardiomyopathy, including cocaine and methamphetamine.

Imaging Studies

• Chest radiography
• • Cardiomegaly may be observed. The absence of cardiomegaly on chest radiograph decreases the likelihood of heart failure (negative LR = 0.33; 95% CI, 0.23-0.48).
  • Depending on the severity of disease and the degree of medical control, signs of pulmonary edema, such as cephalization of pulmonary vasculature, Kerley B lines or, in the most severe cases, interstitial infiltrates, may be observed.
  • The presence of pulmonary vascular congestion and interstitial edema on chest radiograph increases the likelihood of acute decompensated heart failure about 12-fold (positive LR = 12.0; 95% CI, 6.8-21.0).
• Echocardiography
• • Echocardiography may be indicated in the ED when the cause of cardiac decompensation in the presence of findings suggestive of failure (eg, JVD) is unclear. In this setting, the differential diagnosis may include pulmonary embolism or cardiac tamponade, and secondary findings associated with pulmonary embolism such as right ventricular distention or pericardial effusion with tamponade may be seen.
  • Echocardiography is used to help differentiate dilated cardiomyopathy from restrictive and hypertrophic cardiomyopathy.
  • Dilated chambers and thin walls are the most prominent features of dilated cardiomyopathy.

Other Tests

• Electrocardiography
• • Electrocardiography is helpful in identifying left ventricular enlargement and estimating the other chamber sizes.
  • An electrocardiogram showing atrial fibrillation increases the likelihood of heart failure (positive LR = 3.8; 95% CI, 1.7-8.8). The absence of any electrocardiographic abnormality decreases the likelihood of heart failure (negative LR = 0.64; 95% CI, 0.47-0.88).
  • This is an important screening tool in differentiating ischemic heart disease from dilated cardiomyopathy.

Procedures

• Central venous line or pulmonary artery catheter provides a good measure of filling pressures, and the latter can estimate cardiac output. However, neither has been shown to improve outcomes when used in acute decompensated heart failure.
• Endomyocardial biopsy may be helpful in diagnosing myocarditis, connective tissue disorders, and amyloidosis.

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Prehospital Care

In cases of severe acute failure, EMS personnel may initiate treatment with oxygen, nitrates, and furosemide en route to the hospital. Cardiac monitoring, continuous pulse oximetry, and ECG may also be performed by units with advanced life support (ALS) certification. Further ventilatory support or even intubation may be indicated if the patient is in extremis.

Emergency Department Care

Treatment of dilated cardiomyopathy is essentially the same as treatment of CHF and pulmonary edema; however, obtaining a thorough history from patients with dilated cardiomyopathy helps determine etiology.

• When beginning treatment, administer oxygen, initiate continuous pulse oximetry and cardiac monitoring, and obtain intravenous access.
• Mainstays of medical therapy are preload reduction, afterload reduction, diuresis, and airway support.
• In patients with severe refractory pulmonary edema, a trial of continuous positive airway pressure (CPAP) or bimodal positive airway pressure (BiPAP) may obviate the need for intubation.

Consultations

Consult an internist, an intensivist, or a cardiologist as indicated for admission when a patient has been diagnosed with dilated cardiomyopathy for the first time or for continued inpatient treatment or monitoring. Emergent consultation with a cardiologist may also be indicated for echocardiography in the ED. 

MEDICATION

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Goals of treatment include symptom relief, improved cardiac output, shortened hospital stay, fewer ED visits, reversal of injury process, and decreased mortality.

In 1994, Baker et al reviewed the incidence of thromboembolism in patients with heart failure due to left ventricular systolic dysfunction and found no clinical evidence to support the use of anticoagulants in those patients who were in sinus rhythm.⁶ Therefore, restrict the use of anticoagulants to those patients in atrial fibrillation, with artificial valves, or with known mural thrombus.

In cases of dilated cardiomyopathy secondary to myocarditis, corticosteroids have been suggested to be helpful in decreasing inflammation; however, the Multicenter Myocarditis Treatment Trial showed no benefit in the use of corticosteroids and azathioprine for treatment of biopsy-proven inflammation in dilated cardiomyopathy.⁷ Some smaller uncontrolled studies have shown benefit, but these results have not been confirmed with a controlled study.

Highlights from pertinent literature also are included below.

Drug Category: Angiotensin-converting enzyme (ACE) inhibitors

When treating dilated cardiomyopathy, use ACE inhibitors first. The Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS) group in 1987 showed that the addition of enalapril to the conventional treatment of CHF yielded a 31% reduction in mortality rate at 1 year.⁸ A similar study by Studies of Left Ventricular Dysfunction (SOLVD) investigators in 1991 revealed a 16% risk reduction.⁹ Losartan, an angiotensin receptor blocker, also has been effective in decreasing mortality rates. 

Drug Category: Cardiac glycosides

Foxglove and its derivatives are the oldest treatment of heart failure, but they still have a place in medicine despite recent advances in other drug categories. In 1990, Jaeschke et al did a meta-analysis of 7 double-blind, placebo-controlled trials.¹⁰ The analysis revealed that 1 in 9 patients with CHF showed significant clinical benefit from treatment with digoxin. Note that this was an improvement of symptoms, not a reduction in mortality.

The Digitalis Investigation Group trial demonstrated that digoxin decreases heart failure hospitalizations but has no effect on long-term survival.¹¹

Although little controversy exists as to the benefit of digoxin in patients with symptomatic left ventricular dysfunction and concomitant atrial fibrillation, the debate continues over its role in patients with normal sinus rhythm.

Drug Category: Loop diuretics

Loop diuretics are necessary adjuncts in the medical therapy for heart failure when symptoms are due to sodium and water retention. They are the mainstay of diuretic therapy because they produce significantly more natruresis than other diuretics, particularly in the setting of decreased glomerular rate. They provide symptomatic relief without prolonging life or altering disease course.

Despite clear indications for loop diuretics in the reduction of volume overload, controversy exists regarding their use in acute decompensated failure. No large prospective trial has examined diuretics in acute decompensated heart failure.

Loop diuretics have a tendency to cause hypokalemia and hypomagnesemia; therefore, monitor electrolyte levels and replace as necessary.

Drug Category: Beta-blockers

The most recent and promising research has yielded great reductions in mortality rates when beta-blockers are added to outpatient management of CHF. In 1993, the Metoprolol in Dilated Cardiomyopathy (MDC) study compared patients who had experienced heart failure and were treated with metoprolol in addition to conventional therapies with those who were treated solely with conventional therapies.¹² The study revealed a 34% reduction in primary endpoints (ie, need for heart transplant, death) in those who were treated with metoprolol in addition to conventional therapies.

In 1996, the US Carvedilol Study showed a 65% reduction in mortality in patients with heart failure treated with carvedilol.¹³ Carvedilol acts in 3 ways: as a beta-blocker, an alpha-blocker, and an antioxidant.

The Metoprolol CR/XL Randomized Intervention Trial in CHF (MERIT-HF), the largest trial ever completed using a beta-blocker in heart failure, was performed in 13 European countries and the United States.¹⁴ The results were announced in 1999. MERIT-HF was a randomized, double-blind trial that compared the effects of extended-release metoprolol (metoprolol-XL) with the effects of a placebo on survival and other outcome measures (eg, sudden death, hospitalization for heart failure, quality of life). The trial, which began in 1997 and was scheduled to continue until 2000, closed prematurely following an interim analysis that identified a highly positive effect of metoprolol-XL on all causes of mortality.

A statistically significant 34% reduction in relative risk for total mortality at 1 year was observed; mortality rates were 7.2% in the metoprolol-XL group and 11% in the placebo group (P=0.0062;). Results at the time of study termination also revealed a 38% reduction in cardiovascular mortality, a 41% reduction in sudden death, and a 49% reduction in CHF mortality.¹⁴

Drug Category: Vasodilators

In 1986, the VA Cooperative Study revealed a 36% reduction in mortality risk in patients treated with preload and afterload reducers (ie, isosorbide dinitrate, hydralazine) in addition to conventional heart failure medications.¹⁵

Preload reduction with venodilators is thought to be helpful in acute decompensated heart failure by reducing congestions and minimizing cardiac oxygen demand. Afterload reduction is also thought to be helpful in some patients with acute decompensated heart failure by decreasing myocardial oxygen demand and improving forward flow.

Intravenous nitrate therapy resulted in acute improvement of dyspnea in 2 randomized trials. Similarly, morphine acts as a venodilator, and it central suppresses symptoms of breathlessness; however, no rigorous studies of morphine have been performed in acute decompensated heart failure. Sublingual nitroglycerin spray, nitropaste, and IV nitroglycerin also have been advocated in the treatment of pulmonary edema secondary to CHF.

Drug Category: Potassium-sparing diuretics

Spironolactone acts as an aldosterone receptor blocker and, with concomitant use of ACE inhibitors, helps break the cycle of sodium retention and fluid overload via the renin-aldosterone axis.

In September 1999, Pitt et al published the results of their spironolactone trial. They found that adding 12.5-25 mg of spironolactone per day to a standard treatment regimen for CHF (ie, ACE inhibitor, furosemide, digoxin) yielded a 35% reduction in hospitalization, significant improvements in New York Heart Association (NYHA) functional class, and a 30% reduction in risk of death.¹⁷

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Further Inpatient Care

• The goals of inpatient care are to optimize the balance between intravascular volume and cardiac output and to minimize symptomatology. Determine and reverse specific cause of cardiomyopathy, if possible.

Further Outpatient Care

• Patients with dilated cardiomyopathy should be monitored regularly by their primary care provider or a cardiologist.
• Monitor electrolyte levels.
• Adjust therapy to minimize symptoms.
• Refer patients with NYHA functional class III-IV dilated cardiomyopathy to a cardiothoracic surgeon for possible surgical intervention (eg, partial left ventriculectomy, heart transplant).

In/Out Patient Meds

• ACE inhibitor
• Diuretic
• Digoxin
• Beta-blocker
• Aldosterone antagonist
• Anticoagulant

Deterrence/Prevention

• Many exacerbations can be avoided with a low-sodium diet and medication compliance.

Complications

• Heart failure
• Volume overload
• Pulmonary edema
• Hypoxia
• Cardiogenic shock
• Death

Prognosis

• The Framingham heart study found that approximately 50% of patients diagnosed with CHF died within 5 years.²

Patient Education

• Dietary counseling on a low-sodium diet is a mainstay in the outpatient management of these patients.
• For excellent patient education resources, visit eMedicine's Heart Center. Also, see eMedicine's patient education article Congestive Heart Failure.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Medical/Legal Pitfalls

• Failure to consider a broad differential diagnosis for a patient presenting with apparent heart failure or acute decompensation can lead to overlooking an etiology that may be amenable to acute intervention.
• • Lack of compliance with medications and dietary indiscretion are common causes of decompensation.
  • Arrhythmia, acute coronary syndrome/acute myocardial infarction, valvular disease and sepsis are also potential causes.

ACKNOWLEDGMENTS

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors, Heather Murphy-Lavoie, MD, and Charles Preston, MD, to the development and writing of this article.

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

1. Heart Disease and Stroke Facts. Dallas: American Heart Association; 2006.
2. McKee PA, Castelli WP, McNamara PM, Kannel WB. The natural history of congestive heart failure: the Framingham study. N Engl J Med. Dec 23 1971;285(26):1441-6. [Medline].
3. La Vecchia L, Mezzena G, Zanolla L, Paccanaro M, Varotto L, Bonanno C, et al. Cardiac troponin I as diagnostic and prognostic marker in severe heart failure. J Heart Lung Transplant. Jul 2000;19(7):644-52. [Medline].
4. Peacock WF, Emerman CE, Doleh M, Civic K, Butt S. Retrospective review: the incidence of non-ST segment elevation MI in emergency department patients presenting with decompensated heart failure. Congest Heart Fail. Nov-Dec 2003;9(6):303-8. [Medline].
5. Wang CS, FitzGerald JM, Schulzer M, Mak E, Ayas NT. Does this dyspneic patient in the emergency department have congestive heart failure?. JAMA. Oct 19 2005;294(15):1944-56. [Medline].
6. Baker DW, Wright RF. Management of heart failure. IV. Anticoagulation for patients with heart failure due to left ventricular systolic dysfunction. JAMA. Nov 23-30 1994;272(20):1614-8. [Medline].
7. Mason JW, O'Connell JB, Herskowitz A, Rose NR, McManus BM, Billingham ME. A clinical trial of immunosuppressive therapy for myocarditis. The Myocarditis Treatment Trial Investigators. N Engl J Med. Aug 3 1995;333(5):269-75. [Medline].
8. Swedburg K, CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). The CONSENSUS Trial Study Group. N Engl J Med. Jun 4 1987;316(23):1429-35. [Medline].
9. The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med. Aug 1 1991;325(5):293-302. [Medline].
10. Jaeschke R, Oxman AD, Guyatt GH. To what extent do congestive heart failure patients in sinus rhythm benefit from digoxin therapy? A systematic overview and meta-analysis. Am J Med. Mar 1990;88(3):279-86. [Medline].
11. Rich MW, McSherry F, Williford WO, Yusuf S, Digitalis Investigation Group. Effect of age on mortality, hospitalizations and response to digoxin in patients with heart failure: the DIG study. J Am Coll Cardiol. Sep 2001;38(3):806-13. [Medline].
12. Waagstein F, Bristow MR, Swedberg K, Camerini F, Fowler MB, Silver MA, et al. Beneficial effects of metoprolol in idiopathic dilated cardiomyopathy. Metoprolol in Dilated Cardiomyopathy (MDC) Trial Study Group. Lancet. Dec 11 1993;342(8885):1441-6. [Medline].
13. Packer M, Bristow MR, Cohn JN, Colucci WS, Fowler MB, Gilbert EM. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group. N Engl J Med. May 23 1996;334(21):1349-55. [Medline].
14. MERIT-HF Trial. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet. Jun 12 1999;353(9169):2001-7. [Medline].
15. Cohn JN, Archibald DG, Ziesche S, Franciosa JA, Harston WE, Tristani FE, et al. Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration Cooperative Study. N Engl J Med. Jun 12 1986;314(24):1547-52. [Medline].
16. Taylor AL, Ziesche S, Yancy C, Carson P, D'Agostino R Jr, Ferdinand K. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med. Nov 11 2004;351(20):2049-57. [Medline].
17. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. Sep 2 1999;341(10):709-17. [Medline].
18. Abelmann WH. Classification and natural history of primary myocardial disease. Prog Cardiovasc Dis. Sep-Oct 1984;27(2):73-94. [Medline].
19. Agostini D, Belin A, Amar MH, Darlas Y, Hamon M, Grollier G, et al. Improvement of cardiac neuronal function after carvedilol treatment in dilated cardiomyopathy: a 123I-MIBG scintigraphic study. J Nucl Med. May 2000;41(5):845-51. [Medline].
20. Allen LA, O'Connor CM. Management of acute decompensated heart failure. CMAJ. Mar 13 2007;176(6):797-805. [Medline].
21. Alonso-Martinez JL, Llorente-Diez B, Echegaray-Agara M, Olaz-Preciado F, Urbieta-Echezarreta M, Gonzalez-Arencibia C, et al. C-reactive protein as a predictor of improvement and readmission in heart failure. Eur J Heart Fail. Jun 2002;4(3):331-6. [Medline].
22. American Heart Association. Heart disease and stroke statistics - 2004 update. Dallas, TX: American Heart Association; 2003.
23. Arbustini E, Morbini P, Pilotto A, Gavazzi A, Tavazzi L. Genetics of idiopathic dilated cardiomyopathy. Herz. May 2000;25(3):156-60. [Medline].
24. Azevedo VM, Albanesi Filho FM, Santos MA, Castier MB, Tura BR. How can the echocardiogram be useful for predicting death in children with idiopathic dilated cardiomyopathy?. Arq Bras Cardiol. Jun 2004;82(6):505-14. [Medline].
25. Berger R, Huelsman M, Strecker K, Bojic A, Moser P, Stanek B, et al. B-type natriuretic peptide predicts sudden death in patients with chronic heart failure. Circulation. May 21 2002;105(20):2392-7. [Medline].
26. Binanay C, Califf RM, Hasselblad V, O'Connor CM, Shah MR, Sopko G, et al. Evaluation study of congestive heart failure and pulmonary artery catheterization effectiveness: the ESCAPE trial. JAMA. Oct 5 2005;294(13):1625-33. [Medline].
27. Bristow MR, Gilbert EM, Abraham WT, Adams KF, Fowler MB, Hershberger RE, et al. Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure. MOCHA Investigators. Circulation. Dec 1 1996;94(11):2807-16. [Medline].
28. Chizzola PR, Freitas HF, Caldas MA, da Costa JM, Meneghetti C, Marinho NV, et al. Effects of carvedilol in heart failure due to dilated cardiomyopathy. Results of a double-blind randomized placebo-controlled study (CARIBE study). Arq Bras Cardiol. Mar 2000;74(3):233-42. [Medline].
29. Chung P, Hermann L. Acute decompensated heart failure: formulating an evidence-based approach to diagnosis and treatment (part I). Mt Sinai J Med. Mar 2006;73(2):506-15. [Medline].
30. Cohen N, Muntoni F. Multiple pathogenetic mechanisms in X linked dilated cardiomyopathy. Heart. Aug 2004;90(8):835-41. [Medline].
31. Cohn JN, Johnson G, Ziesche S, Cobb F, Francis G, Tristani F, et al. A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med. Aug 1 1991;325(5):303-10. [Medline].
32. Cotter G, Metzkor E, Kaluski E, Faigenberg Z, Miller R, Simovitz A, et al. Randomised trial of high-dose isosorbide dinitrate plus low-dose furosemide versus high-dose furosemide plus low-dose isosorbide dinitrate in severe pulmonary oedema. Lancet. Feb 7 1998;351(9100):389-93. [Medline].
33. Cuffe MS, Califf RM, Adams KF Jr, Benza R, Bourge R, Colucci WS, et al. Short-term intravenous milrinone for acute exacerbation of chronic heart failure: a randomized controlled trial. JAMA. Mar 27 2002;287(12):1541-7. [Medline].
34. Di Lenarda A, Sabbadini G, Salvatore L, Sinagra G, Mestroni L, Pinamonti B, et al. Long-term effects of carvedilol in idiopathic dilated cardiomyopathy with persistent left ventricular dysfunction despite chronic metoprolol. The Heart-Muscle Disease Study Group. J Am Coll Cardiol. Jun 1999;33(7):1926-34. [Medline].
35. Eichhorn EJ. Medical therapy of chronic heart failure. Role of ACE inhibitors and beta-blockers. Cardiol Clin. Nov 1998;16(4):711-25, ix. [Medline].
36. Eichhorn EJ. The paradox of beta-adrenergic blockade for the management of congestive heart failure. Am J Med. May 1992;92(5):527-38. [Medline].
37. Etoch SW, Koenig SC, Laureano MA, Cerrito P, Gray LA, Dowling RD. Results after partial left ventriculectomy versus heart transplantation for idiopathic cardiomyopathy. J Thorac Cardiovasc Surg. May 1999;117(5):952-9. [Medline].
38. Fatkin D. Guidelines for the diagnosis and management of familial dilated cardiomyopathy. Heart Lung Circ. Feb 2007;16(1):19-21. [Medline].
39. Fedak PW, Smookler DS, Kassiri Z, Ohno N, Leco KJ, Verma S, et al. TIMP-3 deficiency leads to dilated cardiomyopathy. Circulation. Oct 19 2004;110(16):2401-9. [Medline].
40. Felker GM, Hu W, Hare JM, Hruban RH, Baughman KL, Kasper EK. The spectrum of dilated cardiomyopathy. The Johns Hopkins experience with 1,278 patients. Medicine (Baltimore). Jul 1999;78(4):270-83. [Medline].
41. Gilbert EM, Abraham WT, Olsen S, Hattler B, White M, Mealy P, et al. Comparative hemodynamic, left ventricular functional, and antiadrenergic effects of chronic treatment with metoprolol versus carvedilol in the failing heart. Circulation. Dec 1 1996;94(11):2817-25. [Medline].
42. Harrison A, Morrison LK, Krishnaswamy P, Kazanegra R, Clopton P, Dao Q, et al. B-type natriuretic peptide predicts future cardiac events in patients presenting to the emergency department with dyspnea. Ann Emerg Med. Feb 2002;39(2):131-8. [Medline].
43. Heart Failure Society of America. Executive summary: HFSA 2006 Comprehensive Heart Failure Practice Guideline. J Card Fail. Feb 2006;12(1):10-38. [Medline].
44. Hermida-Prieto M, Monserrat L, Castro-Beiras A, Laredo R, Soler R, Peteiro J, et al. Familial dilated cardiomyopathy and isolated left ventricular noncompaction associated with lamin A/C gene mutations. Am J Cardiol. Jul 1 2004;94(1):50-4. [Medline].
45. Hjalmarson A, Kneider M, Waagstein F. The role of beta-blockers in left ventricular dysfunction and heart failure. Drugs. Oct 1997;54(4):501-10. [Medline].
46. Lotze U, Egerer R, Tresselt C, Glück B, Dannberg G, Stelzner A, et al. Frequent detection of parvovirus B19 genome in the myocardium of adult patients with idiopathic dilated cardiomyopathy. Med Microbiol Immunol. May 2004;193(2-3):75-82. [Medline].
47. Läer S, Mir TS, Behn F, Eiselt M, Scholz H, Venzke A, et al. Carvedilol therapy in pediatric patients with congestive heart failure: a study investigating clinical and pharmacokinetic parameters. Am Heart J. May 2002;143(5):916-22. [Medline].
48. Marius-Nunez AL, Heaney L, Fernandez RN, Clark WA, Ranganini A, Silber E, et al. Intermittent inotropic therapy in an outpatient setting: a cost-effective therapeutic modality in patients with refractory heart failure. Am Heart J. Oct 1996;132(4):805-8. [Medline].
49. Maron BJ, Towbin JA, Thiene G, Antzelevitch C, Corrado D, Arnett D, et al. Contemporary definitions and the classification of the cardiomyopathies. Circulation. 2006;113:1807-16. [Medline].
50. McMahon CJ, Nagueh SF, Eapen RS, Dreyer WJ, Finkelshtyn I, Cao X, et al. Echocardiographic predictors of adverse clinical events in children with dilated cardiomyopathy: a prospective clinical study. Heart. Aug 2004;90(8):908-15. [Medline].
51. Medical letter on drugs and therapeutics. Drugs for chronic heart failure. Med Lett Drugs Ther. Oct 11 1996;38(985):92-4. [Medline].
52. Mestroni L, Rocco C, Vatta M, Miocic S, Giacca M. Advances in molecular genetics of dilated cardiomyopathy. The Heart Muscle Disease Study Group. Cardiol Clin. Nov 1998;16(4):611-21, vii. [Medline].
53. Metra M, Giubbini R, Nodari S, Boldi E, Modena MG, Dei Cas L. Differential effects of beta-blockers in patients with heart failure: A prospective, randomized, double-blind comparison of the long-term effects of metoprolol versus carvedilol. Circulation. Aug 1 2000;102(5):546-51. [Medline].
54. Mobini R, Maschke H, Waagstein F. New insights into the pathogenesis of dilated cardiomyopathy: possible underlying autoimmune mechanisms and therapy. Autoimmun Rev. Jun 2004;3(4):277-84. [Medline].
55. National Center for Health Statistics. National hospital discharge survey 2001. Available at http://www.cdc.gov/nchs/data/hdasd/sr13_156t11.pdf.
56. Packer M, Colucci WS, Sackner-Bernstein JD, Liang CS, Goldscher DA, Freeman I, et al. Double-blind, placebo-controlled study of the effects of carvedilol in patients with moderate to severe heart failure. The PRECISE Trial. Prospective Randomized Evaluation of Carvedilol on Symptoms and Exercise. Circulation. Dec 1 1996;94(11):2793-9. [Medline].
57. Pfeffer MA, Braunwald E, Moye LA, Basta L, Brown EJ Jr, Cuddy TE, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators. N Engl J Med. Sep 3 1992;327(10):669-77. [Medline].
58. Pitt B, Segal R, Martinez FA, Meurers G, Cowley AJ, Thomas I. Randomised trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE). Lancet. Mar 15 1997;349(9054):747-52. [Medline].
59. Publication Committee for the VMAC Investigators. Intravenous nesiritide vs nitroglycerin for treatment of decompensated congestive heart failure: a randomized controlled trial. JAMA. Mar 27 2002;287(12):1531-40. [Medline].
60. Publication Committee for the VMAC Investigators (Vasodilatation in the Management of Acute CHF). Intravenous nesiritide versus nitroglycerin for treatment of decompensated congestive heart failure: a randomized controlled trial. JAMA. 2002;287:1531-40. [Medline].
61. Ramires FJ, Mansur A, Coelho O, Maranhao M, Gruppi CJ, Mady C, et al. Effect of spironolactone on ventricular arrhythmias in congestive heart failure secondary to idiopathic dilated or to ischemic cardiomyopathy. Am J Cardiol. May 15 2000;85(10):1207-11. [Medline].
62. Richardson P, McKenna W, Bristow M, Maisch B, Mautner B, O'Connell J, et al. Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of cardiomyopathies. Circulation. Mar 1 1996;93(5):841-2. [Medline].
63. Ripa S, Ripa R, Giustiniani S. Are failured cardiomyopathies a zinc-deficit related disease? A study on Zn and Cu in patients with chronic failured dilated and hypertrophic cardiomyopathies. Minerva Med. Nov-Dec 1998;89(11-12):397-403. [Medline].
64. Riza Erbay A, Turhan H, Aksoy Y, Senen K, Yetkin E. Activation of coagulation system in dilated cardiomyopathy: comparison of patients with and without left ventricular thrombus. Coron Artery Dis. Aug 2004;15(5):265-8. [Medline].
65. Rusconi P, Gomez-Marin O, Rossique-Gonzalez M, Redha E, Marin JR, Lon-Young M, et al. Carvedilol in children with cardiomyopathy: 3-year experience at a single institution. J Heart Lung Transplant. Jul 2004;23(7):832-8. [Medline].
66. Shannon JJ. Medical therapy for congestive heart failure: 1994 update. Resid Staff Physician. 1994;13-20.
67. Silver MA, Horton DP, Ghali JK, Elkayam U. Effect of nesiritide versus dobutamine on short-term outcomes in the treatment of patients with acutely decompensated heart failure. J Am Coll Cardiol. Mar 6 2002;39(5):798-803. [Medline].
68. Silver MA, Maisel A, Yancy CW, McCullough PA, Burnett JC Jr, Francis GS, et al. BNP Consensus Panel 2004: A clinical approach for the diagnostic, prognostic, screening, treatment monitoring, and therapeutic roles of natriuretic peptides in cardiovascular diseases. Congest Heart Fail. Sep-Oct 2004;10(5 Suppl 3):1-30. [Medline].
69. Suma H, Isomura T, Horii T, Sato T, Kikuchi N, Hosokawa G. Isolated effect of partial left ventriculectomy for dilated cardiomyopathy: a case report. J Cardiol. May 1999;33(5):273-7. [Medline].
70. The Captopril-Digoxin Multicenter Research Group. Comparative effects of therapy with captopril and digoxin in patients with mild to moderate heart failure. JAMA. Jan 22-29 1988;259(4):539-44. [Medline].
71. The SOLVD Investigators. Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med. Sep 3 1992;327(10):685-91. [Medline].
72. Tintinalli JE. Emergency Medicine. In: A Comprehensive Study Guide. 4^th ed. McGraw-Hill Co: 1996:354-367.
73. Towbin JA, Bowles NE. Genetic abnormalities responsible for dilated cardiomyopathy. Curr Cardiol Rep. Sep 2000;2(5):475-80. [Medline].

Article Last Updated: Sep 30, 2008