Introduction

The term cardiomyopathy means disease within the muscles of the heart which can be categorized as primary (only confined to the heart) or secondary (systemic, affecting other areas of the body).¹ This group of disorders is classified by their structural and functional abnormalities that make cardiomyopathies the leading cause of cardiac failure and heart transplantation in children.^2,4 Although rare, with the incidence of primary cardiomyopathies affecting 1 in 100,000 young individuals below the age of 20, this disorder can become progressively severe and sometimes fatal.^3,8 However, the majority of pediatric cardiomyopathy (PC) cases are characterized by negative impacts on physical growth and development in childhood. 

Overview of pediatric cardiomyopathy

There are different variations of cardiomyopathy in children:

Dilated cardiomyopathy (DCM) is the most common form of PC, accounting for approximately 50% of all cases. In DCM, the left ventricle is often dilated and so systolic function declines as a result of difficulties with pumping blood. Two-thirds of DCM cases are classed as ‘idiopathic’, meaning the cause is unknown, which is suspected to be attributed to hereditary (inherited) abnormalities.⁵

Hypertrophic cardiomyopathy (HCM) is the most common primary PC, where the left ventricle experiences hypertrophy (thickening of the ventricle wall), with an incidence making up 34.2% of PC cases. This disease morphology also causes pumping difficulty.^1,4

Restrictive cardiomyopathy (RCM) is defined by impaired filling of the ventricles due to an increased stiffening of the heart muscles but no hypertrophy. It is the least common compared to DCM and HCM, only representing 2% to 5% of cases.^1,2,4

Arrhythmogenic cardiomyopathy (AC), also known as arrhythmogenic right ventricular dysplasia (ARVD), is characterized by frequent increase of heart rate (tachyarrhythmia) and sudden cardiac death (SCD).

The causes of cardiomyopathy in children are diverse, but primary pediatric cardiomyopathy (PPC) mainly points to genetic factors.⁴ The majority of DCM and HCM cases are genetically passed down from parents in an autosomal dominant pattern, causing alterations (mutations) in structural proteins that play a big role in heart muscle function and structure.^1,4 These include sarcomeric, cytoskeletal and desmosomal proteins, each making up a different aspect of muscle fibers and their links to one another.⁷

Secondary pediatric cardiomyopathy (SPC) is not inherited, but rather acquired through another condition. Potential causes can include:

• Metabolic disorders – Pompe disease, Danon disease^1,2,5,7
• Neuromuscular diseases – Duchenne and Becker muscular dystrophy (DMD/BMD)^5,7
• Infections – acute viral myocarditis, coxsackievirus (hand, foot and mouth disease), adenovirus infection^1,10
• Toxic exposures – cardiotoxic agents such as those used in chemotherapy e.g. doxorubicin, cyclophosphamide¹

Children with PC may present general symptoms like fatigue, exercise intolerance, feeding difficulty and overall failure to thrive, indicating poor growth and development.²

Impact on physical growth

Poor growth and weight gain in children or ‘failure to thrive’ (now most commonly referred to as growth faltering) is most notable in infants and young children with DCM and RCM. This is due to newborns and infants with DCM commonly exhibiting dyspnea (shortness of breath), which is associated with abnormal feeding behaviours.^2,4 

Most commonly in PPC, the skeletal muscles can be affected due to mutations that contribute to diminished physical function and muscle mass, limiting affected children from participating in physical activity. Older children and adolescents typically demonstrate high fatigability (tiredness) and exercise intolerance related to breathing difficulties and muscle atrophy (loss of muscle mass).^2,4,10 On the other hand, delayed skeletal maturation and growth restriction is specifically seen in pediatric patients who have undergone heart transplants due to cardiomyopathy before the age of seven.¹²

Hormonal abnormalities, particularly with growth hormones like human growth hormone HGH can be expected with PC. Growth hormones are involved in myocardial (heart muscle) growth and function. In PC, HGH levels in the blood are reduced, leading to abnormal myocardial growth – thickening, dilation etc.¹¹ 

Impact on neurodevelopment and cognitive outcomes

The impact of SPC is systemic and extends beyond heart and physical function. The disorder also imposes a risk to the central nervous system, especially the brain which may experience hypoperfusion (insufficient blood flow to tissues) and hypoxia (low oxygen in tissues) that affect the brain’s functioning and hence cognition.^1,2,4

Memory, attention or speech deficits are not usually linked to PC, however psychosocial functioning seems to be the most strained in children aged five years old and over, demonstrating lower scores than normal.⁹

Cardiomyopathies, which result in a dysfunction and restructuring of heart muscles alter blood flow, therefore increasing risk of clot formation and embolic events. This is particularly the case with DCM and HCM.^4,5 

Strategies to reduce impact

The diagnosis and management of PC involves many complex strategies to achieve early detection and specialized support for the patients. 

Genetic testing and screening is crucial for early diagnosis and should be offered to all genotype-positive patients and at-risk relatives.⁶ With precise genetic testing, the mode of inheritance is determined -often autosomal dominant- and the patient can be informed of the predicted prognosis (likely outcome) of the disease.³ Genetic counselling for parents is also often recommended as it can help guide treatment decisions and extend life expectancy by improving quality of life.¹

Echocardiographic screening is the primary diagnostic technique used typically for HCM and DCM in both pediatric and adult patients.^5,6 It is highly commended for individuals susceptible to secondary PC with pre-existing conditions associated with SPC such as metabolic disorders and neuromuscular diseases. Annual screening is done for susceptible children from infancy to five years of age, with screening continuing every two years for those aged six to 12 years and every three years for teenagers and older.⁵

As for treating issues with growth and development, there are various approaches for management. As poor feeding is a common symptom of PC, resulting in nutritional deficiencies, nutritional support is widely provided.¹ Supplements like L-carnitine and coenzyme Q10 are useful in reversing heart muscle complications.² To maintain adequate physical functioning, recreational exercise with moderate intensity is highly encouraged for all ages to promote healthy heart functioning and lifestyle.⁶ 

Psychological support like specialized social services and counselling, may also be recommended for pediatric patients and immediate families affected with the illness, as parents of PC patients are often significantly emotionally impacted.⁹ 

Cardiac transplantation is an optimal treatment (most effective yet drastic and usually last-resort treatment) considered when traditional therapy is unsuccessful for recurrent DCM and RCM, as these induce chronic heart failure in pediatric patients and is.² Although this is a highly invasive and high-risk procedure, some studies show survival rates are as promisingly high as 92% survival at 5 years post-transplantation.⁵

Summary 

Pediatric cardiomyopathy is a rare but serious disorder of the heart muscle that can be acquired through inherited genetic mutations or secondary to systemic diseases and other external factors.

The main types of cardiomyopathy, including dilated, hypertrophic, restrictive and arrhythmogenic, cause structural changes in cardiac muscles which result in cardiac dysfunction, which further extends to growth failure and in some cases, challenges in cognitive functioning.

Early diagnosis is attained through genetic testing and echocardiographic screening is then combined with nutritional, physical and psychological support for management. These strategies are key to improving PC prognosis and the quality of life in pediatric patients.