Dilated cardiomyopathies

Dilated cardiomyopathy is characterised by ventricular chamber enlargement and contractile dysfunction with normal left ventricular wall thickness. The right ventricle may also be dilated and dysfunctional. Dilated cardiomyopathy is the most frequent reason for heart transplantation.

It is a biochemical abnormality of cardiac muscle and is a diagnosis of exclusion, particularly excluding ischaemic and hypertensive heart disease, although the clinical effects may be identical.

There are separate articles which discuss Cardiomyopathies, Hypertrophic Cardiomyopathy, Arrhythmogenic Right Ventricular Cardiomyopathy and Restrictive Cardiomyopathy.

Epidemiology¹

• It is difficult to know the true prevalence but it is estimated at around 1 in 2,500.

• Genetic inheritance arises in 35% of patients .

• Mutations in 60 genes have been associated with dilated cardiomyopathy² .

• Genes that encode for sarcomeric, cytoskeletal, nuclear membrane, dystrophin-associated glycoprotein complex and desmosomal proteins are the principal genes involved³ .

• It usually occurs in adults aged 20-60 years, but children can also be affected.

• It is more common in males than in females⁴ .

• Some genotypes occur more often in African-Americans than in Caucasians⁵ .

Aetiology

Finding an underlying cause can often be very difficult, especially as many patients have more than one underlying risk factor. Causes may include:

• Ischaemia.

• Idiopathic cause.

• Genetic cause - usually autosomal dominant with incomplete penetrance, although there are rare X-linked cases (including the rare Barth syndrome).

• Alcohol dependency.

• Thyrotoxicosis.

• Autoimmune - eg, rheumatoid arthritis, SLE.

• Drug abuse - eg, cocaine, amfetamines and heroin.

• Drugs - eg, phenothiazines.

• Peripartum cardiomyopathy.

• Infiltrative: haemochromatosis, amyloidosis, glycogen storage disease.

• Sarcoidosis.

• Chronic Chagas' cardiomyopathy.

• HIV infection.

• Other infectious disease - eg, adenovirus, Coxsackievirus, cytomegalovirus, toxoplasmosis, Lyme disease.

• Keshan disease (due to selenium deficiency) - prevalent in areas where the soil is low in selenium⁶ .

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 third and/or fourth heart sound.

• Fatigue, weakness, and exercise intolerance are often progressive.

• A viral prodrome with malaise, flu-like illness or chest pain from antecedent myocarditis may be present.

• Atrial fibrillation may develop.

• A family history should be used to identify affected relatives for clinical and genetic assessment.

Investigations⁴

Investigations may include the following:

• CXR: 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.

• B-type natriuretic peptide (BNP) can be of clinical use in diagnosis, management, and prognosis of patients, especially those with heart failure.

• Investigations to determine the underlying cause may be required.

• Cardiac catheterisation: usually shows raised filling pressure.

• Coronary arteriography: usually shows normal vessels.

• Endomyocardial biopsies: biopsies expose patients to unnecessary risks and should only be undertaken to exclude specific heart muscle disorders - eg, myocarditis, amyloidosis, sarcoidosis or haemochromatosis.

Management⁴

Management is aimed at improving cardiac function, treating symptoms and preventing complications. The treatment is therefore the same as for treating heart failure.

• 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 beta-blockers 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.

• Beta-blockers: 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.

• Anticoagulation: for patients with atrial fibrillation, prosthetic heart valve, or known mural thrombus.

• Implantable cardioverter defibrillator: reduces risk of sudden death in high-risk patients.

• Cardiac resynchronisation can be considered.

• Mitral annuloplasty or valve replacement can improve symptoms in patients with severe mitral regurgitation.

• In patients with recurrent ventricular tachycardia, catheter ablation may be beneficial⁷ .

• Response to medical therapy may be disappointing and, particularly in the young, heart transplantation or left ventricular assist devices may be required. Transplant has excellent functional results. One study of patients with familial dilated cardiomyopathy reported survival rates of 91% at one year and 80% at five years⁸ .

• Stem cell therapy improves left ventricular ejection fraction, and reduces left ventricular end-systolic volume and left ventricular end-diastolic chamber size in patients with dilated cardiomyopathy. Further research is needed regarding effect of stem cell therapy in this group of patients⁸ .

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.

Prognosis⁴

• Prognosis is related to the severity of disease at initial presentation.

• Measures that affect prognosis are fluid and salt restriction, compliance with medication and exercise.

• Five-year survival for patients with dilated cardiomyopathy is about 50%. Mitral regurgitation or diastolic dysfunction is associated with a worse prognosis.

• Peripartum cardiomyopathy is associated with a high morbidity and mortality, and diagnosis is often delayed⁹ .

• Cardiac arrhythmia is often a potential trigger of sudden cardiac death.

• Accurate molecular genetic diagnosis is critical for achieving effective prognostic determination and appropriate cardiac care¹⁰ .

Prevention

• Avoidance of excessive alcohol intake and abstinence from cocaine.

• Early diagnosis and management of any other potential cause.