Pediatric heart failure: A focus on low-income countries

Abstract

Heart failure (HF) in the pediatric population is unique because it involves heterogeneous groups of diseases, including congenital and acquired conditions. The etiology of HF varies with age and sociodemographic origin. In low-income countries, unoperated congenital heart diseases are common, leading to a high prevalence of infants with HF and older children with Eisenmenger syndrome. In addition, rheumatic heart diseases are prevalent, leading to advanced HF in children. Infectious diseases such as tuberculosis and schistosomiasis add to the burden of heart diseases through complications, including pericarditis and pulmonary hypertension. In tropical regions, cardiomyopathies (e.g., endomyocardial fibrosis) have unique causes that have been linked to tropical parasitic infections. The management of pediatric HF is constrained by challenges such as late diagnosis and poor access to medical and interventional therapies. Point-of-care ultrasound holds promise for improving early diagnosis, but appropriate training is required for its use. This study reviews the diagnosis and management of HF, with an emphasis on the limitations encountered in low-resource settings.

Key Words: Low-income countries; Heart failure; Pediatric; Congenital heart disease; Sociodemographic index; Cardiomyopathy

Core Tip: Heart failure in children has variable congenital and acquired etiologies depending on the age and sociodemographic origin. In limited resource settings, heart failure is mostly due to unrepaired congenital heart disease, rheumatic heart disease and unique cardiomyopathies. Management in such settings is complicated by late presentation and limited access to medical and interventional therapies.

INTRODUCTION

Heart failure (HF) is a clinical manifestation of various disorders that lead to the inability of the heart to adequately meet the metabolic demands of body tissues. Kantor et al[1] define HF specifically as “failure of the heart to supply blood to either the systemic or pulmonary circulation at an appropriate rate of flow, or to receive venous return at an appropriate filling pressure, resulting in adverse effects on the heart, the circulation, and the patient”. HF may occur at any stage of development, from the fetal period through adolescence, with etiologies that are age specific and vary widely across geographical regions. In children living in resource-limited settings, HF has distinct causes - predominantly unoperated congenital heart diseases (CHD), rheumatic and tropical heart diseases, coupled with inadequate access to medical and interventional therapies. This review highlights the burden and unique features of pediatric HF in resource-limited settings.

EPIDEMIOLOGY

Pediatric HF affects approximately 83 out of 100000 individuals, with an estimated incidence of 0.87 per 100000, and a mortality rate reaching 7%[2]. The global incidence and outcomes of HF are highly influenced by limited access to pediatric cardiology and cardiac surgical services in low-income countries. Although mortality from CHD has declined globally, this improvement is largely confined to regions with a relatively high sociodemographic index (SDI), with most CHD-related deaths continuing to occur in low- and middle-SDI areas[3]. This discrepancy in mortality has been attributed to a combination of medical and sociodemographic factors, which are summarized in Table 1. Given the high birth rates in developing countries - approximately 30 per 1000 live births per year in Africa - it is estimated that over 1.3 million infants are born with CHD annually worldwide. Of these, approximately 90% (approximately 500000 children) are born in regions with suboptimal or no cardiac care services[4]. Notably, complications of unoperated CHD, such as Eisenmenger syndrome, remain common in low-income countries in which cardiac care services are absent or limited, in stark contrast to developed countries, where timely cardiac surgical intervention is routinely available[5]. Rheumatic heart disease (RHD), which has nearly disappeared from most high-income countries, persists as the leading cause of acquired heart disease among children and young adults in many low- and middle-income countries[6].

Table 1 Factors leading to disparity in congenital heart diseases management between high- and low-income countries.

High income countries	Middle/Low income countries[2,4,6]
Prenatal factors
Lower birth rate and less consanguinity	High birth rate and more consanguinity
Preconception folic acid	No routine folic acid supplements
Antenatal diagnosis (echocardiography)	Sparsity of antenatal echo
Immediate postnatal factors
Hospital delivery and postnatal examination	Home deliveries are common
Neonatal pulse oximetry screening	No neonatal pulse oximeter screening due to early discharge
Well baby clinic
School screening	Late diagnosis
Access to medical and interventional treatment
Timely access to interventions (cardiac catheterization and surgery)	Poor access to prostaglandins
Availability of technical settings and personnel for high-risk interventions	Poor access to timely interventions
Medical insurance coverage	Few neonatal interventions
	The majority of patients/procedures are not covered by insurance
Follow up
Access to timely follow up	Poor follow up rate
Access to medical and interventional treatment	Poor access to and compliance with medications
The burden of RHD
Low prevalence of rheumatic heart disease	High prevalence of RHD

RHD: Rheumatic heart disease.

ETIOLOGY

The etiology of HF in children is largely age dependent. The major causes of pediatric HF and the influence of sociodemographic factors across different age groups are illustrated in Figure 1. The causes of HF can be broadly classified into four categories: CHD, acquired heart disease, cardiomyopathy (CMP), and pulmonary hypertension (PHT). These categories often overlap, as CMP may be congenital in origin or occur concurrently with CHD. Similarly, PHT may be a primary cause of HF or develop as a secondary complication of CHD, mitral valve disease, or CMP.

Figure 1 Age-specific etiology of heart failure and the impact of low sociodemographic status. CHD: Congenital heart diseases.

HF due to CHD

The global prevalence of CHD is estimated at 18 per 1000 live births, making it the most common cause of HF in infants[7]. CHD leading to HF can be classified into unrepaired, repaired, and palliated categories, with unrepaired CHD being the most prevalent among infants in low-SDI countries.

Unrepaired CHD

HF in the neonatal period may result from critical CHD, such as coarctation of the aorta and hypoplastic left heart syndrome, which are ductus arteriosus-dependent lesions requiring prompt diagnosis and immediate administration of prostaglandin E1, a life-saving medication. Unfortunately, this medication is often unavailable in many low-SDI countries. Furthermore, neonatal open-heart surgery is rarely performed in such settings due to the high level of operative and postoperative care required[5]. Consequently, mortality among neonates with critical CHD remains unacceptably high in such countries. Among infants with CHD, the most common cause of HF is left-to-right shunts. The timing of surgical repair/palliation is crucial, as left-to-right shunt lesions can progress to elevated pulmonary artery pressure and irreversible pulmonary vascular obstructive disease (Eisenmenger syndrome) if left untreated. Due to the constraints outlined in Table 1, delayed diagnosis and management contribute to a high mortality rate - as high as 6% for simple left-to-right shunts. Notably, many of these challenges persist in several middle-income countries[8].

Repaired CHD

Patients who have undergone CHD repair may still develop HF due to early or late postoperative residual lesions. Pulmonary regurgitation following tetralogy of Fallot repair is a common complication, particularly after transannular patch repair of the right ventricular outflow tract. Although pulmonary regurgitation may be well tolerated for many years, HF can develop later due to progressive right ventricular dilatation, eventually leading to ventricular dysfunction and arrhythmias in adolescence and adulthood. Definitive management requires pulmonary valve implantation, which may be performed surgically or via a transcatheter approach. However, both approaches impose a significant financial burden on patients in low-resource settings[9].

Palliated CHD - Glenn/Fontan operations

Functionally univentricular hearts account for approximately 2% of CHD and require staged palliation, typically involving the Glenn and Fontan cavopulmonary anastomoses. Advances in the management of the Fontan procedure have significantly improved survival, with projections estimating that the global population living with a Fontan circulation will reach approximately 7.2 per 100000 individuals by 2045[10]. HF following a Fontan operation is associated with the unique hemodynamic characteristics of Fontan circulation: Chronically elevated central venous pressure, persistently reduced ventricular preload, and postoperative arrhythmias[11]. The management of patients with univentricular heart requires a multidisciplinary team and access to advanced HF care - resources that are often limited or unavailable in low-resource settings. Although initial palliative procedures such as aortopulmonary shunts, ductus arteriosus stenting, and the Glenn operation can be performed in low-resource settings, outcomes remain guarded. In a study conducted in South Africa - a middle-income country - involving 154 patients with univentricular hearts, the overall mortality rate was 18%, although the reported mortality rate may be an underestimate, as nearly 30% of the patients were lost to follow-up[12]. A more recent study in the same country reported an improved mortality rate of 3%; however, complications occurred in 57% of the cases, and only 37% of the patients successfully proceeded to the second stage of palliation[13]. However, less favorable outcomes have been reported for Angola, with the mortality rate for single-ventricle palliation being as high as 45%[14]. Deciding whether to operate on complex cardiac lesions remains a major challenge in resource-limited settings; therefore, each case must be carefully assessed, considering the high risks associated with multiple complex surgeries and the limited postoperative care infrastructure.

HF due to acquired heart disease

Acute myocarditis: Acute myocarditis (AM) results from inflammation of the cardiomyocytes, leading to myocardial edema and necrosis. It is most commonly caused by viral infections, particularly parvovirus B19 and human herpes viruses, with an estimated incidence of 0.8-1.0 per 100000 population[15].

Tropical parasitic infections such as trypanosomiasis and amebiasis may also be associated with myocarditis via direct myocardial invasion by the parasite or the triggering of a localized inflammatory response[16]. The clinical presentation of AM typically includes acute-onset HF following a viral prodrome, while severe cases may present with cardiogenic shock requiring intensive cardiac management including mechanical circulatory support. In affected patients, echocardiography often reveals a dilated, poorly contracting left ventricle, mimicking the appearance of dilated CMP (DCM). Cardiac magnetic resonance imaging has emerged as a sensitive diagnostic tool capable of differentiating AM from chronic DCM[17]. The management of AM focuses on standard HF therapy, supportive care, and close monitoring for signs of low cardiac output. The prognosis of AM in children remains guarded, although the outcomes are generally better than those of DCM. In a study involving biopsy-confirmed cases, up to 48% of the patients had persistent echocardiographic systolic dysfunction, 19% required heart transplantation within a 3-year follow-up period, and 7% died[18]. In low-income countries, delayed diagnosis - especially in severe forms of AM - often leads to early mortality. Furthermore, limited access to intensive care unit facilities contributes to comparatively poor outcomes and high mortality rates.

RHD: RHD is a sequela of acute rheumatic fever, a nonsuppurative inflammatory reaction following infection with group A Streptococcus. Although RHD has virtually disappeared from high-income countries, it remains highly prevalent in low- and middle-income countries, affecting an estimated 40 million patients worldwide, and with a particularly high incidence in Oceania, Central Africa, and South Asia. RHD is recognized as the most common cause of acquired HF in young populations in these regions[19]. The hallmark of RHD is valvulitis, which predominantly affects mitral and aortic valves, leading primarily to regurgitation and subsequent complications such as HF, arrhythmias, stroke, and death. The introduction of point-of-care ultrasound (POCUS) as a screening and diagnostic technique in resource-limited settings has facilitated the detection of RHD at subclinical stage. Such stages may regress or stabilize with timely and appropriate interventions[20,21]. The management of advanced RHD involves medical therapy for HF and arrhythmias; however, this approach is largely palliative, as surgical or interventional procedures are often required in severe cases. Surgical valve repair in children presents significant challenges due to their relatively small cardiac structures and a persistent inflammatory milieu, both of which contribute to disease recurrence. Consequently, the long-term outcomes of rheumatic mitral valve repair in children are generally less favorable than in adults. Nonetheless, valve repair is preferred over valve replacement, as the latter necessitates lifelong anticoagulation - a major challenge for children in resource-limited settings[22]. Over the last decade, collaborative efforts between high- and low-income countries have led to a substantial increase in RHD research. These initiatives have produced evidence-based management guidelines and promoted echocardiographic screening as an essential tool for the diagnosis, prevention, and control of RHD[23].

Pericarditis: Acute pericarditis is most commonly viral in origin and is characterized by the acute onset of chest pain and echocardiographic evidence of variable degrees of pericardial effusion. It is typically self-limiting and resolves without residual cardiac dysfunction. However, HF may also occur in patients with pericarditis complicated by massive effusions that result in pericardial tamponade. Tuberculous pericarditis occurs in approximately 1%-2% of patients with tuberculosis and remains prevalent in low-income countries[24]. It presents with pericardial effusion, often without other features of tuberculosis. On an echocardiogram, the effusion often appears fibrinous. Detection of Mycobacterium tuberculosis in pericardial fluid is challenging; therefore, a therapeutic trial employing antitubercular therapy is commonly employed in suspected cases from endemic regions. The addition of corticosteroids to the antitubercular medications during the first 6 weeks of treatment has been shown to minimize the risk of progression to constrictive pericarditis[25], the late stage of the disease, which is characterized by pericardial calcification and is best managed by surgical pericardiectomy. In a study involving 44 children with tuberculous pericarditis, 9% developed constrictive pericarditis, while 90% presented with cardiac tamponade. The causative organism was identified by smear or culture in only 18% of cases[26]. A recent meta-analysis of 125 cases of tuberculous pericarditis reported a mortality rate of approximately 5%, notwithstanding appropriate antitubercular therapy[27].

Pediatric CMP: CMP refers to a myocardial disorder characterized by structural and/or functional abnormalities of the heart muscle in the absence of coronary artery disease, hypertension, valvular disease, or CHD[28]. CMP is a leading cause of HF in children and young adults worldwide, with an estimated prevalence of 1 in 500 and 1 in 250 for the hypertrophic and dilated types, respectively[29]. The disease exhibits wide phenotypic and genetic patterns and is classified as either primary (idiopathic, familial, or genetic) or secondary to systemic conditions such as metabolic disorders. The World Health Organization classifies primary CMP morphologically into DCM, hypertrophic CMP (HCM), and restrictive CMP (RCM) - a framework that has been widely adopted because of the consistent correlation of its categories with clinical and echocardiographic presentations[30]. Another phenotypic variant is left ventricular non-compaction CMP, which is characterized by prominent myocardial trabeculations and deep intertrabecular recesses, and may present asymptomatically or with ventricular arrhythmias, HF, or sudden cardiac death[31].

Endomyocardial fibrosis - a distinct form of RCM - is prevalent in tropical and subtropical regions. Although its etiology remains poorly understood, it is thought to be associated with parasitic infections[32]. Endomyocardial fibrosis typically affects boys aged 8-15 years and presents with right-sided or biventricular HF. Echocardiography is diagnostic, demonstrating apical fibrosis with right ventricular obliteration and markedly dilated atria. Left ventricular involvement occurs in approximately 20% of cases, often causing mitral regurgitation[33]. Although surgical intervention may improve survival, the overall prognosis remains poor, as no curative treatment exists[34].

Up to 32% of patients with primary CMP have an identifiable genetic etiology, while rare pathogenic variants are present in up to 56% of affected individuals[35]. Data from low-resource countries remains limited. In a cohort of 665 patients older than 13 years from Southern Africa, DCM accounted for 72% of the cases, followed by HCM (10%) and RCM (5.8%)[36]. Similarly, a study of 146 Sudanese children with CMP reported neonatal onset in 4% of the study cohort and familial disease in 11%, with DCM being the most prevalent CMP subtype (67%)[37]. Few studies have investigated the genetic basis of pediatric CMP in low-resource settings. A study conducted in Egypt involving 14 children with HCM identified 10 rare variants in eight of the participants - two pathogenic variants (8.3%) in MYBPC3 and MYH7, and eight variants of uncertain significance in MYBPC3, TTN, VCL, MYL2, CSRP3, and RBM20[38]. Notably, reversible causes of CMP - such as structural heart disease, mineral and trace element deficiencies, and metabolic disorders (e.g., hypocalcemia, thyroid disorders, and carnitine or selenium deficiencies) - should be carefully investigated and treated. Malnutrition remains a vital contributor to CMP in resource-limited settings, with deficiencies in selenium, thiamine, and niacin reported to be associated with CMP[39]. Optimum nutrition and micronutrient supplementation are recommended for affected children. Overall, CMP carries a guarded prognosis, as treatment is mainly supportive. Although certain genetic forms of CMP may be amenable to targeted therapy, such treatments are often costly and inaccessible in low-income settings. For HCM, disopyramide - a class 1A antiarrhythmic agent with an adverse inotropic effect - has been shown to improve symptoms of left ventricular outflow tract obstruction[40]. When used as an adjunct to beta-blockers, it may reduce the need for high-risk interventions that are not readily available in low-resource settings.

PHT: PHT is defined as a mean pulmonary artery pressure of ≥ 20 mmHg and encompasses a wide range of etiologies across the pediatric age spectrum, from neonates to adolescents[41]. It is estimated that approximately 80% of patients with PHT reside in tropical regions. The high prevalence of RHD, combined with the substantial number of unoperated CHD cases progressing to Eisenmenger syndrome, creates a dual burden of pre- and postcapillary PHT in these populations. In addition, several diseases prevalent in low-resource settings, including schistosomiasis, sickle cell disease, and human immunodeficiency virus infection, are well-recognized causes of PHT[42]. Diagnostic cardiac catheterization poses significant risks in settings with limited access to intensive care units. Furthermore, the unavailability of inhaled nitric oxide in many low-resource settings hinders the performance of vasoreactivity testing, which is essential for guiding management. The high cost of pulmonary vasodilators further limits treatment options for patients in low-income countries. Consequently, outcomes in these settings remain poor, as PHT is a chronic and progressive disease requiring specialized centers for advanced therapy.

DIAGNOSIS

Pediatric HF is primarily a clinical diagnosis based on medical history and physical examination supported by chest radiography. The use of cardiac biomarkers such as troponin and brain natriuretic peptide, although well established in adults, is less common in pediatrics due to age-specific variations in interpretation. In resource-limited settings, biomarker use is further restricted by cost and availability issues[43]. Echocardiography remains essential for establishing the underlying cause of HF and assessing the extent of structural and functional cardiac abnormalities. POCUS has gained widespread popularity as a rapid and reliable tool for structural and functional cardiac assessment, particularly in emergency and intensive care settings. Evaluation of inferior vena cava dilatation and respiratory variation using POCUS provides valuable information on intravascular volume status and facilitates immediate decision-making regarding diuretic therapy in patients with HF[44]. Lung POCUS has emerged as a safer and more informative alternative to chest radiography for diagnosing pneumothorax, pulmonary edema, and pleural effusions[45]. Building upon its extensive use in RHD screening, expanding POCUS to primary and secondary care could significantly enhance HF diagnosis in resource-limited settings. In CHD diagnosis, POCUS has demonstrated a sensitivity of approximately 70% and a specificity of 98%[46]. However, consensus on its application in CHD screening is lacking, largely due to the need for comprehensive echocardiographic training. With appropriate capacity-building initiatives, POCUS could be effectively utilized for CHD diagnosis in settings where standard echocardiography is unavailable, thereby bridging a critical diagnostic gap. Cardiac computed tomography is a valuable tool for diagnosing CHD, particularly in evaluating pulmonary arteries, pulmonary veins, and coronary artery anomalies. Cardiac magnetic resonance imaging offers distinct advantages, including a detailed assessment of ventricular volumes, ejection fraction, and regional function. It plays a central role in diagnosing myocardial diseases and in assessing right ventricular function following the tetralogy of Fallot repair[47]. However, the application of these techniques in low-income countries is limited by high equipment costs and the need for specialized training in pediatric cardiac imaging. Innovative approaches such as vendor-supported training and remote mentorship could facilitate the adoption of these advanced diagnostic services despite infrastructural constraints[48]. In pediatric populations, cardiac catheterization is reserved for specific indications, including hemodynamic evaluation of shunts and PHT, as well as for interventional procedures such as CHD repair and mitral commissurotomy. In resource-limited settings, pediatric cardiac catheterization is constrained by multiple challenges, including limited access to disposable supplies, a shortage of trained medical and paramedical personnel, and the limited availability of cardiac intensive care units. These challenges may be mitigated through structured training programs and regional or international twinning partnerships with advanced cardiac centers abroad[49].

TREATMENT

Medical treatment

The variable etiologies of HF across different pediatric age groups and sociodemographic distributions present a significant challenge to the development of universal guidelines for pediatric HF management. Alternatively, clinical guidelines need to be tailored to specific subgroups, considering the distinct needs associated with age, underlying diagnosis, and socioeconomic context. Due to the relatively small patient population, the heterogeneity of the etiologies, and the ethical and practical constraints of invasive monitoring and testing of new medications in children, most large-scale clinical trials on HF therapy have recruited only adults. Table 2 summarizes the medications currently used to manage pediatric HF[50-56].

Table 2 Medications used for pediatric heart failure.

Drug/group	Evidence for pediatric HF	Recommendation
Renin-angiotensin-aldosterone system	PANORAMA study[50] did not show advantage of sacubitril/valsartan over ACEI	Angiotensin converting enzyme inhibitors are used routinely
Inhibitors: Captopril, enalapril, lisinopril and sacubitril/valsartan	A study involving 23 patients showed improvement of EF and LV dimensions with a low dose[51]	The United States Food and Drug Administration has approved sacubitril/valsartan pediatric HF > 1 year of age
β-blockers	There is not enough evidence to support or discourage the use[52]	May be used with close observation
Carvedilol
Mineralocorticoid receptor antagonists (spironolactone)	Evidence mainly derived from adult studies[53]	Used in HF
Digoxin	Evidence mainly derived from adult studies	Used as 3rd or 4th line in CHF
		Used in tachyarrhythmias
Diuretics	Evidence mainly derived from adult studies[54]	Loop diuretics are used for fluid overload
Furosemide		Addition of other diuretics enhances loop diuretic effect
Spironolactone
Thiazides
Metolazone
Sodium-glucose cotransporter-2 inhibitors	Use in children was found to be safe and well tolerated in a meta-analysis[55]	Awaiting more studies to be approved
Ivabradine	Evidence of improvement in HF[56]	Can be used in children

HF: Heart failure; ACEI: Angiotensin converting enzyme inhibitors; EF: Ejection fraction; LV: Left ventricle; CHF: Congestive heart failure.

Interventional therapy

A recent survey of pediatric cardiac services across African countries revealed that only 40% of the 45 countries that responded possessed both pediatric cardiology and cardiac surgical facilities. A severe shortage of trained personnel was also evident, with ratios of pediatric cardiothoracic surgeons and pediatric cardiologists estimated at 0.04 and 0.17 per million population, respectively. The cost of cardiac surgery, averaging approximately 5000 United States dollars, remains unaffordable for most families and is only partially covered by government insurance in most countries. Currently, Africa has only eight level 4 or 5 institutions, representing just 9% of the continent’s facilities, with Western and Central Africa notably lacking any centers at these levels[56]. These findings underscore the urgent need to strengthen cardiac care capacity through the targeted training of physicians and surgeons, expansion of pediatric cardiac services, and enhanced government support for comprehensive insurance coverage for children with heart disease in low-income countries.

Supportive treatment

High-caloric oral feeding is essential in managing cardiac cachexia in infants, and nasogastric tube feeding may be recommended in selected cases. Vitamin and micronutrient supplementation is also critical for addressing associated nutritional deficiencies. Social and psychological support play an essential role for both children and their families, who must often grapple with prolonged illness, recurrent hospitalizations, and disruptions to schooling and parental employment. Optimal management of pediatric HF requires a multidisciplinary heart team comprised of social workers, psychologists, and nutritionists, supported by standardized protocols. However, such collaborative care is frequently constrained by a shortage of trained personnel. In resource-limited settings, physicians are often compelled to assume multiple roles, leading to fragmented care and diminished effectiveness of pediatric HF management.

The challenges of HF management in resource-limited settings are illustrated in Figure 2, and potential strategies to address them are outlined.

Figure 2 Limitations of management of heart failure in limited resource settings and potential solutions. HF: Heart failure.

CONCLUSION

Pediatric HF has a heterogeneous etiology that encompasses both structural and functional abnormalities and exhibits considerable sociodemographic variations. The patterns of HF in low-resource countries differ markedly from those in high-income countries, with a higher prevalence of unoperated CHD, RHD, PHT, and tropical CMP in low-resource compared to high-income countries. Management in these settings is further constrained by limited access to pediatric cardiac services, contributing to elevated mortality rates. The use of POCUS in the diagnosis of pediatric HF is expected to gain wider adoption, enhancing early detection and management. Future efforts should focus on national commitments to improving pediatric cardiac care services and fostering global collaboration to strengthen capacity building and training initiatives.