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Dilated Cardiomyopathy

Essentials

  • Typical symptoms in the early stages include dyspnoea on exertion, arrhythmias and sometimes a feeling of pressure or a long-lasting, mild pain on the chest that is not related to exercise. As the disease progresses, the patient will develop heart failure and associated oedema.
  • Asymptomatic incipient dilated cardiomyopathy may first manifest itself as an enlarged heart shadow on a chest x-ray or an abnormal ECG finding.
  • If previously undiagnosed heart failure or left ventricular dilatation is noted, the patient must undergo echocardiography and, depending on the results, further investigations to identify the cause of heart failure.
  • Pharmacological therapy is similar to that used in heart failure of any aetiology; ACE inhibitors and angiotensin receptor blockers as well as beta blockers are the drugs of choice; a combination of valsartan and sacubitril is a newer preparation.
  • The identification of atrial fibrillation and initiation of anticoagulation is important in order to prevent cardiogenic embolism and worsening of the heart failure.
  • Dilated cardiomyopathy is in at least 30% of the cases hereditary, i.e. running in families.
    • The most common mode of inheritance is autosomal dominant inheritance but in gene defect carriers the disease usually manifests only at middle age.
    • It is possible in some cases to detect the disease mutation by using extensive gene panel analyses. Therefore, it is recommended that the patient is referred to a unit of clinical genetics or to a cardiology department with experience in investigating the genetic background of diseases for the consideration of genetic testing.
    • Using extensive gene panels, a definite or probable disease mutation has been found in about 30% of the cases in the Helsinki University Central Hospital. Particularly familial cases should be referred for an assessment of the need for genetic testing but also in cases that seem to be non-familial, a gene defect can be found in a fair share of patients.
    • If a gene defect is not found, it does not always exclude the possibility of a hereditary disease, since not all disease genes are yet known. In such cases it is recommend that the first-degree relatives of the patient are referred to a cardiologist for clinical assessment and particularly echocardiography, if no obvious cause is identified for dilated cardiomyopathy, such as a history of chemotherapy.
    • Children are to be referred to a paediatric cardiologist for examination.

Pathophysiology and predisposing factors

  • Prevalence in adults is 1:500-1:3 000. In children the disease is considerably less common than in adults.
  • Hereditary causes account for 30-50% of cases.
    • Familial autosomal inheritance pattern is the most common, but other patterns have also been described.
    • There are numerous underlying disease genes, most of which are related to the contractile or structural proteins of the cardiac muscle cells. The titin (TTN) and lamin A/C (LMNA) genes are for the moment the most important disease genes.
      • Mutations of the titin gene leading to production of truncated protein have been reported to explain about one fifth of the disease cases.
      • Cardiomyopathy associated with the lamin A/C gene mutations starts with a conduction defect and is characterised by a difficult clinical picture.
    • Variants of the desmoplakin gene (DSP) may be associated, to a varying degree, with dysfunction of the left and/or right ventricle, but also with a significant predisposition to ventricular arrhythmias and troponin release events that may resemble, for example, myocarditis.
    • The disease may be genetic, even if the family history is negative, for example at the emergence of a new mutation.
    • Duchenne and Becker type muscular dystrophy may be associated with X-linked cardiomyopathy.
  • Sequela of myocarditis: viruses and virus-induced immunological response
    • The majority of these viruses probably cause common infections in the population.
  • Systemic connective tissue disease (rheumatic arthritis, SLE, polymyositis)
  • Inflammatory myocardial diseases, such as cardiac sarcoidosis, giant cell myocarditis or lymphocytic myocarditis may lead to a clinical picture that resembles dilated cardiomyopathy.
  • Excessive and long-term consumption of alcohol may be the principal cause of dilated cardiomyopathy or a significant predisposing factor. Excessive alcohol consumption impairs left ventricular ejection fraction in carriers of titin gene truncating variants.
  • Metabolic causes: hyperthyroidism, hypothyroidism, diabetes, obesity, particularly as contributing factors. Metabolic storage diseases (haemochromatosis, amyloidosis and sarcoidosis) often lead to restrictive cardiomyopathy, with diastolic dysfunction as the main symptom.
  • Cardiotoxic legal or illegal drugs: doxorubicin, cyclophosphamide, fluorouracil, cocaine
    • The delay in the appearance of symptoms is frequently several years or longer.
    • Anthracycline-induced cardiomyopathy is associated with the cumulative dose of the drug, the presence of other myocardial disorders and the age of the patient.
    • When cardiotoxic drugs or irradiation of the heart area are used in the treament of patient's cancer, consulting a cardiologist familiar with cardio-oncology should be considered, concerning the assessment of cardiac pump function, follow-up and cardiac medication.
  • Tachycardia-induced cardiomyopathy may result from tachycardia that persists for a long time, often for several months, most commonly atrial flutter or fibrillation with fast ventricular response. In infants, a very rapid supraventricular tachycardia may lead to sudden heart failure.
  • Peripartum cardiomyopathy is a disorder that is diagnosed during late pregnancy or the puerperium.
    • For example, disease mutations in titin gene may cause heart failure during pregnancy. In peripartum cardiomyopathy genetic testing is warranted, especially because the child may have inherited the potential gene defect.
  • Idiopathic: no cause is identified. This type may also be genetic; if the patient presents with a new mutation, the family history for cardiomyopathy will be negative.

Signs and symptoms

  • Dilated cardiomyopathy at an asymptomatic or oligosymptomatic stage may manifest itself as an enlarged heart shadow on a chest x-ray ) or an abnormal ECG finding. The disease may also be found by echocardiography when an asymptomatic patient requests to be investigated because of a positive family history.
  • Symptoms
    • Common symptoms are dyspnoea on exertion and arrhythmias.
    • Chest pains feeling like weight on the chest may last for hours or even days, not directly associated with exercise.
    • In more advanced stages, heart failure will lead to oedema and weight gain due to an accumulation of fluid.
  • Pulmonary oedema may develop quickly if dilated cardiomyopathy has progressed unnoticed and the patient develops e.g. fast atrial fibrillation or severe infection, such as pneumonia.
  • Dilated cardiomyopathy may not be noted until the patient presents with a stroke; untreated dilated cardiomyopathy combined with atrial fibrillation may lead to cardiogenic embolism and paralysis.
  • Dilated cardiomyopathy may be diagnosed in association with serious ventricular arrhythmia, e.g. when the patient is resuscitated from ventricular fibrillation

Examination, ECG and laboratory findings

  • Blood pressure is often normal or low.
  • Tachycardia (e.g. sinus rhythm 90-100/min at rest) is a common sign of uncontrolled heart failure.
  • Gallop rhythm: often S3 or S4
  • A systolic murmur caused by secondary mitral regurgitation as a consequence of left ventricle dilatation may be heard near the apex of the heart.
  • ECG is in most cases abnormal, but the changes are non-specific.
    • PQ interval may be prolonged
    • Q waves
    • Left bundle branch block or other conduction disturbance
    • ST and T wave changes
    • P-terminal force (PTF)
    • Left ventricular hypertrophy
    • Atrial or ventricular ectopic beats
  • Atrial fibrillation is common in patients with dilated cardiomyopathy.
  • Particularly in severe heart failure, the patient may experience episodes of ventricular tachycardia, which may cause syncope or even sudden death. If the patient gives a history of presyncope or syncope, a 24-hour ECG recording should be carried out in order to obtain a better picture of the underlying rhythm.
  • In the early stages, a chest x-ray will show an enlarged heart shadow; pulmonary congestion will become evident when heart failure develops.
  • When the patient develops heart failure plasma NT-proBNP concentration will increase.
  • In some genetic types, the troponin concentration in a blood sample may be either considerably increased from time to time or continuously slightly increased, or there may be some underlying inflammatory cardiac disease.

Diagnosis

  • If previously undiagnosed heart failure or left ventricular dilatation is noted, the patient must undergo echocardiography.
    • With echocardiography it is possible to measure the size of the left ventricle, the thickness of the walls, the systolic and diastolic function as well as to assess the possibility of major valvular defects.
  • Increased plasma NT-proBNP or BNP concentration is suggestive of heart failure, but it may also be mildly increased in some other conditions.
  • Cardiomyopathy can only be diagnosed after other heart diseases with similar presentation (heart failure and dilatation of the heart) have been excluded: hypertensive cardiomyopathy, extensive coronary heart disease, significant valvular defects and congenital heart defects.
    • Extensive coronary heart disease and widespread myocardial infarction may cause dilatation and impaired contractility of the left ventricle, which may resemble dilated cardiomyopathy. Diagnosis can be verified with coronary artery angiography, gamma scan of the myocardial perfusion or CT scan of the coronary arteries.
  • Rare inflammatory myocardial diseases can be investigated with cardiac MRI, PET imaging and, if required, endomyocardial biopsy.

Referral for specialist investigations

  • In non-urgent cases, the patient may be referred from primary care to a specialist outpatient clinic for ultrasound and other investigations.
  • A patient who appears ill should be sent to the emergency department of a hospital with facilities to carry out echocardiography.
  • Further investigations are carried out in specialist medical care as considered necessary in order to determine the aetiology.
    • If alcoholic cardiomyopathy is considered a possibility, the following blood tests are carried out: plasma GT, AST and ALT as well as their ratio, carbohydrate-deficient transferrin (CDT) and erythrocyte-MCV. The presence of potential coronary artery disease can be investigated with a CT coronary angiogram, coronary angiography or myocardial perfusion scintigraphy.
    • Cardiac MRI provides suggestive evidence on whether the condition might be an inflammatory cardiomyopathy, such as cardiac sarcoidosis or giant cell myocarditis, or whether late enhancements would suggest dilated cardiomyopathy. Depending on the results, further investigations, such as myocardial biopsy or PET-CT may be carried out.
    • Myocardial biopsy is a specialist investigation which may be considered in select cases where the illness progresses despite treatment, and where it is considered that the result might change the management, as e.g. in cardiac sarcoidosis or giant cell myocarditis.
      • Cardiac sarcoidosis Sarcoidosis has in the recent years proved to be more common than previously assumed. In some cases it may greatly resemble dilated cardiomyopathy. Also sarcoidosis may be identified by myocardial biopsy.
  • The feasibility of genetic diagnosis is assessed by the specialist physician.

Screening and monitoring of family members

  • The diagnosis of cardiomyopathy is always based on clinical assessment.
  • If the patient has first-degree relatives, who in the case of a genetic disease might be at risk of acquiring the disease, gene panel testing is recommended, organized by a clinical geneticist or a cardiologist familiar with the theme.
  • If an explanatory disease variant is found, the relatives are screened only for that particular variant, and no extensive gene panel testing is performed in all of them.
  • If no obvious cause is identified for dilated cardiomyopathy, such as a history of anthracycline therapy, and no disease mutation is found in genetic investigations, it is recommended that the first-degree relatives of the patient, even if they are asymptomatic, are referred to a cardiologist preferably with expertise in myocardial disorders, principally for the purposes of echocardiography.
  • The age of onset of familial dilated cardiomyopathy shows great variation, although the disease typically starts to become manifest only in persons over 40 years of age.
    • Familial dilated cardiomyopathy may become manifest already in childhood or adolescence, and a paediatric cardiologist should be consulted regarding the children.
  • If the disease risk cannot be excluded by genetic testing, it is recommended that the first-degree relatives of the patient are examined occasionally, even if the findings were normal at the initial investigation.
    • Follow-up frequency may vary according to the clinical situation. A typical follow-up interval is 1-3 years from childhood to 20 years of age and 2-5 years from 20 years to 50-60 years of age.
  • Genetic diagnosis is possible in some cases to verify the aetiology or to identify at-risk relatives.
    • The feasibility of laboratory DNA analysis should be considered jointly by a geneticist and a cardiologist with expertise in myocardial disorders or a paediatric cardiologist.
    • In the cases where the familial defective gene has been identified, there is naturally no need to continue the monitoring of family members who do not harbour the defective gene.

Treatment Interventions for Treating Peripartum Cardiomyopathy

  • Treatment should target the underlying cause, e.g. in tachycardia-induced cardiomyopathy
  • Lifestyle advice
    • Abstinence from alcohol
    • Smoking cessation
    • Weight reduction if the patient is overweight
  • Treatment of dilated cardiomyopathy is similar to that used in heart failure. A combination of valsartan and sacubitril is available as the most recent drug for heart failure.
    • ACE inhibitors or, if they are not suitable, angiotensin receptor blockers are the drugs of choice, and they both improve prognosis.
    • A diuretic if congestion is evident. Diuretics are used as symptomatic treatment, and an attempt should be made to reduce the dose as soon as the other medication takes effect.
    • Beta-blockers will improve the prognosis of patients with heart failure. The effects of metoprolol, carvedilol and bisoprolol are the best documented.
    • Digoxin may be used in atrial fibrillation to slow the ventricular response rate and in severe failure to alleviate symptoms.
    • Spironolactone is used in severe heart failure. The risk of renal failure and hyperkalaemia associated with its use must be borne in mind.
    • Patients with dilated cardiomyopathy are anticoagulated
      • virtually always when the patient has persistent atrial fibrillation or flutter, unless there are contraindications
      • after consideration if the left ventricular contractility is markedly impaired.
    • Beta-blockers and amiodarone are the safest choice for the treatment of both atrial and ventricular arrhythmias in patients with impaired left ventricular function.
  • Implanted devices Implantable Cardiac Defibrillators in Nonischaemic Cardiomyopathy
    • A conventional pacemaker Cardiac Pacemakers and Monitoring Their Function for bradycardia
    • An implantable cardioverter defibrillator (ICD, Implantable Cardioverter-Defibrillator (ICD)) may be used in order to prevent the occurrence of life threatening ventricular arrhythmias.
    • In severe failure where there is asynergy in left ventricular contractility, the situation may in some cases be improved with biventricular pacing. All three functions, i.e. ICD, biventricular pacemaker and antibradycardia pacemaker may be found in a single device.
  • Ventricular assist device or heart transplantation is resorted to primarily when
    • heart failure causes severe symptoms and continues to progress despite conventional care
    • the patient is under 70 years of age and otherwise healthy; the age limit is not absolute, and the patent's overall situation is taken into consideration in decision making.

Follow-up

  • Patients will typically attend a hospital outpatient clinic every 3-12 months for a check-up.
  • In between times, patients usually attend their own health clinic for INR measurements, management of renal failure etc. During the visits the following should be observed:
    • the patient's general health: continuous loss of weight and muscle wasting indicate an alarmingly severe failure
    • signs of heart failure (are there signs of fluid retention?)
    • the patient's heart rhythm.
      • Diagnosing atrial fibrillation and starting anticoagulation is of prime importance in the prevention of cardiogenic embolism.
  • If necessary, a specialist physician should be consulted if the patient's condition shows signs of deterioration. This is of particular importance in patients whose follow-up visits take solely place in the primary health care because the disease was initially assessed to be mild.
  • For evaluation of work capacity, an examination by a cardiologist is often requested. Functional capacity is usually measured by exercise ECG or ergospirometry (cardiopulmonary exercise testing, CPET). E.g. possible proneness to arrhythmias is taken into account when assessing the cardiac status.

Prognosis

  • The prognosis of the disease has improved with the introduction of improved pharmacological therapy and implantable devices.
  • Medication usually markedly improves the patient's condition, and the stable phase may last for several years.
  • Despite medication, left ventricular contractility will often gradually worsen and arrhythmias that affect the patient's functional capacity may occur, e.g. atrial fibrillation may become a permanent rhythm.
  • It might be difficult to assess the prognosis for an individual patient.
  • Unfavourable prognostic signs include poor left ventricular function at diagnosis and advanced age.

References

  • Charron P, Arad M, Arbustini E et al. Genetic counselling and testing in cardiomyopathies: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J 2010;31(22):2715-26. [PubMed]

Evidence Summaries ⬆