Epidemiology

• The prevalence is 40-50 cases per 100,000.^[2]
• Genetic inheritance arises in 30-48% of patients.^[3]
• It accounts for between 1 in 50 and 1 in 25 cases of heart failure.^[4]
• Usually occurs in adults aged 20-60 years.
• More common in males.
• Occurs more often in African-Americans than in Caucasians.

Aetiology

It can be primary (genetic, mixed or predominantly familial non-genetic, or acquired) or secondary:

• Ischaemia
• Idiopathic
• Genetic - usually autosomal dominant with incomplete penetrance, though there are rare X-linked cases (including the rare Barth syndrome)
• Alcoholism
• Thyrotoxicosis
• Autoimmune
• Tachycardia-induced dilated cardiomyopathy: prolonged tachycardia; atrial fibrillation and atrial flutter with rapid ventricular response are the most common causes
• Drug abuse, eg cocaine, amfetamines and heroin
• Drugs, eg phenothiazines
• Peripartum cardiomyopathy:^[5] uncommon, dilated cardiomyopathy, presenting with heart failure, emboli or arrhythmia. Increased risk in women with pre-eclampsia or multiple births
• Haemochromatosis
• Sarcoidosis^[6]
• Heavy metals including cobalt
• Chronic Chagas' cardiomyopathy^[7]
• HIV infection and exposure to antiretroviral drugs
• Other infectious disease, eg adenovirus, cytomegalovirus, toxoplasmosis, Lyme disease

Presentation

• Clinical presentation ranges from symptomless forms to heart failure, stroke from thromboembolism, arrhythmias, and sudden cardiac death.
• It may present with the effects of emboli before other symptoms appear.
• Most cases of dilated cardiomyopathy present as congestive heart failure: dyspnoea, weakness, fatigue, oedema, raised JVP, pulmonary congestion, cardiomegaly, loud 3rd and/or 4th heart sound.
• Fatigue, weakness, and exercise intolerance are often progressive.
• Atrial fibrillation, ventricular fibrillation.
• Familial dilated cardiomyopathy is associated with gene defects coding for cytoskeletal proteins in 5% of cases.^[2]
• A family history should be used to identify affected relatives for clinical and genetic assessment.

Investigations

The diagnostic criteria for familial dilated cardiomyopathy have been addressed in detail:^[8]

• Chest x-ray: cardiomegaly, pulmonary oedema
• ECG: may show only sinus tachycardia or an intraventricular conduction delay, left bundle branch block, or nonspecific changes in ST and T waves
• Echocardiogram: marked dilation of the left ventricular cavity and reduced systolic and diastolic function. May also show mitral regurgitation, tricuspid regurgitation and mural thrombus
• Biomarkers can be of clinical use in diagnosis, management, and prognosis of patients, especially those with heart failure.^[9] The most widely used markers are B-type natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP). In adults and children, BNP differentiates symptoms related to lung disease from heart failure.^[3]
• Cardiac catheterisation: usually shows raised filling pressure.
• Coronary arteriography: usually shows normal vessels.
• Endomyocardial biopsies: some patients are shown to have specific heart muscle disorders, eg myocarditis, amyloidosis, sarcoidosis or haemochromatosis.^[10]

Management

Management is aimed at improving cardiac function, treating symptoms and preventing complications.

• Loop diuretics and thiazide diuretics: for all symptomatic patients with fluid overload.
• Angiotensin-converting enzyme (ACE) inhibitors: for patients with reduced left ventricular ejection fraction. Angiotensin II receptor antagonists can be used as an alternative. ACE inhibitors and betablockers improve function even if patients are asymptomatic.
• Digoxin: for patients with inadequate response to ACE inhibitors and diuretics and for patients with atrial fibrillation and rapid ventricular rates.
• Betablockers: indicated for all patients as they have been shown to improve survival.
• Spironolactone: also shown to improve survival.
• Nitrates: for patients with diastolic dysfunction and pulmonary congestion.
• Warfarin: for patients with atrial fibrillation or history of systemic or pulmonary embolism.
• Biventricular pacing (using a cardiac resynchronisation device):
  • Can improve symptoms in patients with class III and IV heart failure with marked QRS prolongation.
  • Can improve survival and increase exercise tolerance.
• Implantable cardioverter-defibrillator: reduces risk of sudden death in high-risk patients.^[11]
• Mitral annuloplasty or valve replacement can improve symptoms in patients with severe mitral regurgitation.
• Response to medical therapy may be disappointing and, particularly in the young, heart transplantation (dilated cardiomyopathy is the most common reason for heart transplantation) or left ventricular assist devices may be required. Transplant has excellent functional results and survival rates of 80% at one year and 70% at five years.^[4]
• Research is underway into progenitor cell therapy following initial pilot trials of intracoronary stem cell infusion in acute myocardial infarction.

Complications

• Progression of the disease causes progressive heart failure.
• Associated conduction defects are often present, and there is also a risk of sudden cardiac death from ventricular arrhythmia.

Prognosis

• Prognosis is related to the severity of disease at initial presentation.
• Five-year mortality rate has been estimated at being between 40% and 80%.^[2]
• Adverse prognosis is associated with renal dysfunction, anaemia, broad QRS, left ventricular ejection fraction below 35%, cardiomegaly on chest X-ray, low exercise capacity or poor cardiac reserve during inotropic stimulation, and persistent high left atrial pressure.^[2]

Prevention

• Avoidance of excessive alcohol intake and abstinence from cocaine.
• Early diagnosis and management of any other potential cause.