What Is Paediatric Cardiomyopathy

Paediatric cardiomyopathy is a rare and serious condition which affects the heart muscles in children. Genetic mutations are the dominant cause of paediatric cardiomyopathies. Cardiomyopathy refers to a structural abnormality in the muscle of the heart, primarily affecting a type of muscle cell called myocytes. It is a progressive condition by which the heart muscles (myocardium) become thickened, causing hypertrophy with high morbidity and mortality rates. 40% of children with symptomatic cardiomyopathy typically die within two years or receive a heart transplant.¹

Symptoms can vary from person to person, and in some cases, no symptoms may be present (asymptomatic). Interestingly, there are several different types of cardiomyopathy called subtypes. The subtype depends on which, if any, other parts of the body are involved and if it is ischemic or non-ischemic. Ischemic refers to the lack of blood flow and oxygen to the heart.² As a result, an ischemic cardiomyopathy may result in impaired ability of the heart to pump blood, causing fatigue, irregular or rapid heartbeats (tachycardia), and heart failure.²

Types of paediatric cardiomyopathy

According to the European Society of Cardiology, paediatric cardiomyopathy is classified into dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), and restrictive myopathy (RCM), among others.³ This classification depends on the predominant phenotype, which may become mixed or undulate during the progression of the disease. 

Dilated cardiomyopathy (DCM)

Dilated cardiomyopathy (DCM) is characterised by two main features; ventricular dilation and systolic dysfunction and is the most common type of paediatric cardiomyopathy.³

DCM can be caused by genetic mutations, inborn errors of metabolism or neuromuscular disorders. It can also be triggered by viral infections or through the toxic effects of certain chemotherapies.

Presenting features

Children with DCM, particularly infants, present with a variety of symptoms ranging from feeding issues to cardiovascular blockage, and very rarely, it can trigger sudden death before other symptoms appear. However, older children may be diagnosed before symptoms onset through routine screening; this includes those with a positive family history, neuromuscular disorders, and inborn errors of metabolism.³ Lymphocytic myocarditis is caused by an influx of white blood cells into the heart muscle following a viral infection. . This subtype is hard to diagnose and may appear idiopathic (arising spontaneously) as there is not always a medical history of viral infection, which could be misleading.³

According to data from the Pediatric Cardiomyopathy Registry (PCMR) and Neuro Anaesthesia and Critical Care Society (NACCS), about 71-90% of children with DCM had clinical evidence of congestive heart failure.³ Moreover, in the NACCS DCM cohort, about 2% presented with arrhythmia or exercise intolerance, 5% with sudden cardiac death, and 3% were identified through routine family screening.³

The most common comorbidities associated with DCM related to intensive care unit admissions are hepatic impairment, renal failure, and thromboembolic events (blood clots).³

Natural history

Medical interventions in children with DCM are variable; some cases can be treated with medication, and some require advanced heart failure therapy, including heart transplantation. DCM is the most common reason for heart transplantation in children. The outcomes of children with DCM are highly variable, ranging from full recovery to death or requirement for transplantation. 

Transplant free-survival analysis after diagnosis generally decreases with increasing age at initial diagnosis from 1 year to >10 years, as other risk factors in children with DCM are age-dependent and vary with the severity of cardiac dysfunction.³

Hypertrophic cardiomyopathy (HCM)

Hypertrophic cardiomyopathy (HCM) is a condition characterised by an increase in the number and size of cardiac muscle cells. HCM is defined as biventricular hypertrophy without structural heart abnormalities or increased ventricular overload.³

Aetiologies

Sarcomeric mutations represent the most significant genetic cause in children and adults; these genes encode sarcomeric proteins, which are the major contractile unit of myocytes (cardiac muscle cells). Sarcomeric mutations are easily detectable with a detection rate of about 60%, and are usually diagnosed after the first year of life.³ The distinction between childhood HCM and adult HCM is that childhood HCM can arise from diverse aetiologies (heterogeneous groups) and a spectrum of diseases.

Genetic causes include neuromuscular disorders, malformation syndromes, inborn errors of metabolism, and pathogenic mutation in sarcomeric genes.³

Presenting features

The clinical status of HCM patients can be asymptomatic or symptomatic. In symptomatic cases, the patient may exhibit: 

• Palpitations
• Exercise intolerance
• Cardiac arrest
• Chest pain
• Syncope (loss of consciousness)
• Congestive heart failure (CHF) or arrhythmia is found in 10-15% of cases at presentation.
• Children with inborn genetic errors or malformation syndromes present earlier in life and are at higher risk of congestive heart failure.³
• In childhood HCM, sudden cardiac death is an uncommon initial presentation.³

Natural history

The outcome of childhood HCM is highly dependent on the age at presentation and the underlying aetiology; those diagnosed in the first year of life are at the highest risk of mortality.³ The rate of survival without transplantation was found to be about 90% at 5 years and 78% years at 20 years from initial presentation.³ The worst outcomes arise from those that present with heart failure in infancy.

Factors that increase mortality risk include: REFS

• Noonan syndrome³
• Concentric left ventricular hypertrophy at diagnosis.³
• Increasing left ventricular free wall thickness.³
• Worsening left ventricular systolic function during follow-up.³
• Congestive heart failure is the major cause of early sudden deaths in children with HCM.

Restrictive cardiomyopathy (RCM)

Restrictive cardiomyopathy (RCM) is a rare form of heart muscle disease characterised by abnormal diastolic function with restrictive filling but normal ventricular size, ejection fraction and wall thickness.³ Nearly a quarter of cases with RCM are associated with a family history of cardiomyopathy.

Aetiologies

RCM has overlapping aetiology with several other cardiomyopathy subtypes, as an increasing rate of sarcomeric and non-sarcomeric genetic mutations have been reported. Moreover, a subgroup of RCM combines HCM and RCM characteristics, resulting in a mixed phenotype.³ Additionally, RCM has also been associated with inborn errors of metabolism, skeletal myopathy, and infiltrative disease.³

Presenting features

Early symptoms of RCM are non-specific, including:

• Exercise intolerance 
• General fatigue

Secondary clinical findings of pulmonary venous pressures include REF.

• Pulmonary hypertension
• Hepatomegaly
• Pulmonary oedema
• Peripheral oedema

In the late stages, patients may develop:

• Systolic dysfunction
• Arrhythmias
• Thromboembolic events
• Coronary Ischemia

Late-stage symptoms may result in non-specific syncope (loss of consciousness) symptoms.

Natural history

RCM has the worst outcomes among the other cardiomyopathy forms, with high rates of early referral for transplantation.³ Because it is progressive, patients are at a high risk for sudden death, ventricular arrhythmias, thromboembolism, conduction disorders, and congestive heart failure. 

The 5-year transplant-free survival rate after diagnosis in children with typical RCM is 22%. However, the mixed phenotype group (RCM/HCM) reported a 2-fold higher 5-year transplant-free survival rate.³

Diagnosis of paediatric cardiomyopathies

It is extremely important to evaluate the intrinsic changes of the myocardium as well as monitor heart functions such as systolic and diastolic volume and myocardial growth (atrophy or hypertrophy). Therefore, echocardiography is the cornerstone diagnostic tool in terms of accuracy and reliability to detect cardiomyopathy.^3,4 The studied parameters are left ventricular filling time, E- and A- wave patterns, and wall thickness, among others.⁴ These parameters vary from child to child depending on the type of cardiomyopathy. 
Another significant diagnostic technique is cardiac magnetic resonance as it can highlight other important features and as such, can be used in detecting disease mechanisms, prognosis assessment, and treatment guidance.⁴ Nuclear cardiology has also been shown to be an effective technique in the diagnosis of cardiomyopathies.⁴ Nuclear cardiology studies on myocardial function and cardiac pump function.⁴

Endomyocardial biopsy is a useful diagnostic tool for the evaluation of cardiac pathology and treatment of cardiomyopathies.^3,5 Endomyocardial biopsy, unlike other diagnostic techniques, is an invasive procedure used to detect histologic changes in the heart tissue; thus, it has been associated with complications.3,5 Endomyocardial biopsy should still be selected in certain cases despite the added risks, particularly those cases with diverse underlying disease processes presenting as heart failure. Moreover, the diagnosis of cardiac phosphorylase kinase deficiency can only be done using endomyocardial biopsy, and this can cause certain severe cardiomyopathies.^3,5

Treatment

Adjunct treatments are used to slow the progression of cardiomyopathy, treat associated symptoms such as high blood pressure, and improve heart functions. Also, surgery might be an option in certain cases to improve the function of valves or remove areas of thickened heart muscle. REF In the worst cases, a heart transplant is the only choice during congestive heart failure. 

Medical treatment

• In children with cardiomyopathy, adjunct treatments are essential to correct dehydration and metabolic acidosis; this is typically done by monitoring input and output and even dialysis in some cases.^1,4
• Diuretics, angiotensin-converting enzyme inhibitors and β-blockers are popular treatments for heart failure in dilated cardiomyopathy. ⁴Diuretics help in improving symptoms, whereas angiotensin-converting enzyme inhibitors are observed to prolong survival and improve mortality.⁴
• Carvediol, a β-blocker is the treatment of choice in paediatric dilated cardiomyopathy; it has an additional vasodilating action which improves cardiac functions with minimal adverse effects.¹
• Intravenous infusions of β-blockers and inotropes, including dopamine and dobutamine, improve myocardial function and reverse chronic congestive heart failure for a certain short duration. However, it may cause arrhythmias.⁴
• For children with RCM, vasopressin-receptor antagonists are effective and safe for those with severe congestive heart failure. Unlike in dilated cardiomyopathy, angiotensin-converting enzyme inhibitors should be avoided in RCM due to their potential to reduce systemic blood pressure. Diuretics and digoxin should be used with caution.⁴
• In children with hypertrophic cardiomyopathy, β-blockers and calcium channel blockers are beneficial symptomatic treatments for chest pain and dyspnea, while digitalis and diuretics are found to be rarely beneficial.⁴
• For cases with intracardiac thrombi, with or without symptoms, anticoagulant therapy is used.¹

• In patients with symptomatic arrhythmias and low myocardial contractility, antiarrhythmics and anticoagulants should be considered respectively, particularly amiodarone.¹

Bridging operations

In patients with dilated cardiomyopathy, a Batista procedure, which is a partial left ventriculostomy, has been suggested to sustain patients until they are able to receive a heart transplant. However, further studies in different reports have shown its low safety and effectiveness.

Another operation, called intra-aortic balloon pump support, acts as a temporary device to support heart function and maintain organ perfusion until heart transplantation can take place.1,6 Such mechanical support devices have some main limitations and risks, including risk of infection, noise, batteries needing to be charged frequently, and thromboembolism.^1,6

Cardiac resynchronization therapy is another significant therapy with remarkable outcomes in children with dilated cardiomyopathy, it is an operation that uses a biventricular pacemaker.^1,6

Palliative therapy

Mitral valve repair is a beneficial therapy for selected patients with mitral valve regurgitation, by which the heart valves can’t work properly, the flaps of the mitral valves do not close well, causing a backward flow of blood back to the heart, this method shows promising outcomes.^1,6

Dynamic cardiomyoplasty is an alternative to heart transplantation by which the skeletal muscle from another part of the body is transformed to produce a myocardium-like-fatigue-resistant muscle.^1,6

Cardiac transplantation

Cardiac transplantation is the optimal treatment in patients with DCM or RCM, which induces resistance to chronic heart failure. However, there are limitations, including complications of rejection, availability of a suitable donor, and lifelong immunosuppression. In patients who have received a transplant, survival rates rise to 92% at 5 years.^1,6

Research and advances

Recently, there have been several approaches to finding alternative methods with high safety and efficacy outcomes and without certain limitations. Cellular cardiomyoplasty is an innovative approach to regenerate myocardium using stem cell therapy for the treatment of congestive heart failure.¹ Moreover, investigations have found that insulin-like growth factor I (IGF-I) has remarkable effects in improving cardiac mass and modulation of cardiac apoptosis in patients with cardiomyopathy.¹

Summary

Paediatric cardiomyopathies are a group of myocardial disorders involving complicated pathologies and associated with variable comorbidities, particularly arrhythmias, heart failure, and sudden death. In case pharmaceutical treatments fail to improve cardiac functions, the next step could be surgical operations such as bridging operations, palliative therapy and ventricular septal manoeuvres. Individualised therapy regimens linked to genetic factors and pathogenesis may improve the cardiac function and patient survival rate.