An estimated 15 million children die or become disabled annually by treatable or preventable heart disease in low- and middle-income countries (LMICs). Sadly, for 90% of children with heart disease, treatment is either unavailable, unaffordable, or of suboptimal quality. Global efforts to reduce mortality in children younger than 5 years have focused on reducing death from communicable diseases in LMICs, with little to no attention focusing on pediatric congenital heart disease (CHD) and acquired heart disease. Lack of awareness of CHD and acquired heart disease, access to care, poor health care infrastructure, competing health priorities, and a critical shortage of specialists are important reasons why pediatric heart disease has not been addressed in low-resourced settings.
Global Burden of Pediatric Heart Disease
Heart disease in children has not made any impression on the global health agenda; hence it is little wonder that 90% of the children with heart disease never receive the care they require. Amid a narrative dominated by the acquired heart diseases of adults, predominantly lifestyle related, it is therefore now important to illustrate the full extent of the problems of heart disease in children, defined as a person younger than 18 years.
There are, broadly speaking, two groups of heart disease in children, either congenital or acquired heart diseases. The CHD group embraces all manner of heart defects present at embryologic development of the heart, through fetal life and are present at birth. Of course, they may also be present in the case of a spontaneous abortion or stillbirth, and we know that CHD is an important cause of both. However, included in the CHD definition are also structures normal in fetal life, which ought to close after birth but in some cases have persisted into early childhood. Thus persistence of the arterial duct or an interatrial defect is included in our definition. There are many adults living with CHD, and in well-resourced countries there is evidence to show that through interventions and surgery with impressive survival rates, there are now more adults with CHD than there are children. Arrhythmogenic disease may not always fit perfectly into either group. Certainly the genetics of the prolonged QT syndrome, having been well described, should be included as a form of CHD. This is likewise for Wolff-Parkinson-White syndrome, even though patients invariably become symptomatic years after birth. Acquired heart disease in children includes rheumatic heart disease (RHD), Kawasaki disease, Chagas disease, cardiomyopathy, myocarditis, pericarditis, infective endocarditis, and other infections of the heart. This section focuses on describing the global burden of congenital and RHD because they contribute to the overwhelming majority of burden of pediatric heart disease. The remaining conditions have not been adequately studied from the perspective of defining the global burden.
Global Burden of Congenital Heart Disease
What is meant by the term “burden of disease”? To some it intuitively means the prevalence or incidence of a disease. That being the case, when considering CHD it would seem to be a simple matter of reviewing all the studies of prevalence, including birth prevalence, showing that CHD occurs in approximately 8 per 1000 live-born babies, using estimates of the global population (9 billion) and calculating 72 million persons with heart disease or 1 million born with CHD per year.
To the best of our knowledge, however, for several reasons related to ascertainment and attrition, this simple methodology is likely an oversimplification. A study of 20,307 newborns in India found an overall CHD birth prevalence rate similar to that reported worldwide, at 8.07 per 1000 live births (95% confidence interval [CI], 6.94 to 9.4). Another study from China showed similar results, with 686 having CHD in a cohort of 84,062 births, resulting in an overall incidence of 8.2 per 1000 total births.
Our task is made somewhat easier by the recent Global Burden of Disease (GBD) Study undertaken by the Institute for Health Metrics and Evaluation. This is the most comprehensive worldwide observational epidemiologic study to date. It describes mortality and morbidity from major diseases, injuries, and risk factors to health at global, national, and regional levels. The prevalence of disease at birth and at other ages is a key descriptor to be drawn from this work. The GBD Study is the most important statistical and epidemiologic resource available and includes CHD and acquired heart diseases.
The Institute for Health Metrics and Evaluation has systematically reviewed all available data sources on morbidity and mortality of CHD from 195 countries and territories for inclusion in epidemiologic models. Using the publicly available GBD-Compare visualization tool, the top causes of infant deaths from 1990 to 2016 have been identified for various regions of the world and classified on basis of their sociodemographic index (SDI).
Annual global infant CHD mortality is estimated to be 142,917 (95% CI, 126,267 to 164,297). Communicable diseases are the leading cause of death in infants in low and low-middle SDI countries. In high SDI regions, congenital anomalies and sudden infant death syndrome are the leading causes of death. From 1990 to 2016 the death rate due to communicable diseases decreased by 50% in low SDI regions and 75% in middle SDI regions. The death rate from CHD decreased by 60% in high SDI, 40% in middle SDI, and 20% in low SDI regions. The death rate in low SDI (62 per 100,000) and middle SDI (87 per 100,000) regions remains elevated compared with high SDI regions (20 per 100,000). CHD is now the fifth leading cause of death in infants globally. Despite a lower absolute death rate, CHD accounts for a higher proportion of deaths in middle (13%) and high-middle (16%) SDI regions. If this trend continues, CHD will become a leading cause of infant mortality worldwide.
However, is it sufficient to just estimate numbers of children with heart disease? The noun burden is defined as a load or a misfortune causing hardship or grief. Heart disease in children certainly causes anxiety in most parents and patients, hardship for the child with the disease and for their family and grief for those who have demised either through neglect or perhaps despite treatment. The noun also conveniently denotes obligation, duty, and responsibility. We recognize that society has a duty to care for the sick and an obligation, through a combination of financial arrangements, to pay for that care. Therefore burden denotes the amount or number of children with heart disease but also the cost of care. Those costs, carried by private contribution or from the public purse, differ between countries. However, does the crude average cost for the surgical repair of a simple and common problem (e.g., a ventricular septal defect [VSD]), whether in a low-income country like India or high-income country like the United States, accurately reflect the true burden?
In the less-developed regions of the world, notably Africa and southern Asia, the vast majority of those born with CHD will never receive care for what in better-resourced countries are treatable conditions. Ninety percent of children with heart disease are without access to the care they need to live healthy and productive lives. Congenital heart defects are the most common of all birth defects, occurring in approximately 1 out of 120 births, and the rate of disease is relatively stable across countries and demographics. However, the impact of the disease is heaviest on those countries with both high number of annual births and greatest levels of poverty. Julien Hoffman, writing in 2013 on the “global burden of congenital heart disease,” noted that “Although the incidence of congenital heart disease (CHD) is similar worldwide, the burden of supporting these patients falls more heavily on countries with high fertility rates. Countries with the highest fertility rates tend to have the lowest incomes per capita, thus accentuating the disparity.” Although they all experience the same rate of CHD, the burden these cases have on their respective health system varies by the annual number of births in the country and its level of poverty. When all measures are taken into account, the burden of CHD ranges from Brazil’s 9.7 cases per million gross domestic product (GDP) to 297.5 in Kenya. By comparison, the United States, despite a large number of cases of CHD, has a CHD to GDP ratio of only 2.2, due to their high GDP. This is what we mean when we say that by region, Africa and south Asia have the greatest burden of heart disease. The full socioeconomic impact of the diseases can be measured relative to the environments in which they occur. Higher birth rates and lower economic development mean that the overwhelming global burden of pediatric heart disease falls on the health systems least equipped to deal with it.
The World Health Organization reported the annual years of healthy life lost (2011) due to the disability of CHD at 19.8 million disability-adjusted life years (DALYs). By comparison, childhood cluster diseases (whooping cough, diphtheria, measles, and tetanus) accounted for 23.5 million DALYs. From 2000 to 2012, the burden of childhood cluster diseases decreased by 70%, whereas the DALYs from CHD remained constant.
Global Burden of Rheumatic Heart Disease
The most recent estimated prevalence of RHD based on the GBD data (2015) in all age groups is 33.4 million (95% uncertainty interval [UI], 29.7 to 43.1 million). There were an estimated 319,400 deaths (95% UI, 297,300 to 337,300) or 10.5 million (95% UI 9.6 to 11.5 million) DALYs from RHD globally in 2015. It is estimated that there has been a nearly 50% decline in deaths from RHD globally in 2015 when compared with estimates from 1999. Notwithstanding this decline, there is still a substantial burden in selected regions in South Asia, the Pacific Islands, and Sub-Saharan Africa; many indigenous communities in Asia and Pacific continue to show a high prevalence of rheumatic fever (RF) and RHD.
There are many challenges to obtaining correct estimates of RHD. School-based surveys are the most commonly used methods for estimating RHD prevalence in children and adolescents. Studies using echocardiography-based methods of measuring prevalence in school children have demonstrated a nearly 10-fold higher prevalence of valvar abnormalities, compared with prevalence reported using clinical diagnostic methods. Little is known about the natural history of these asymptomatic cases compared with the smaller number of symptomatic cases that have traditionally been reported.
It is also important to recognize that the worst affected regions with RHD are most difficult to survey often because of a serious deficiencies in primary health care that affect the performance of accurate surveys. Because it is not mandatory to report acute RF or maintain registries in many countries, the incidence of new cases of RF is hard to estimate. Furthermore, it is increasingly obvious that many patients of RHD do not recall discrete episodes of RF.
Pediatric Cardiac Care in Low- and Middle-Income Countries
Low- and middle-income economies are currently classified on the basis of annual gross national income per capita (<$12,736 per capita). The threshold for low-income countries is $1045 or less gross national income per capita. Low- and middle-income groups taken together are also referred to as the developing world.
LMICs are not uniform in terms of their access to health care and therefore development of pediatric heart care. Although there are large parts of Africa and South Asia with high infant and “under-5” mortality and virtually no access to pediatric cardiac care, there are also examples of LMICs such as Sri Lanka and Cuba that have achieved excellent childhood health indices and are now seeking to develop comprehensive and accessible pediatric cardiac care. Furthermore, wide disparities are seen within countries as well. This is particularly true for large and diverse nations such as India and China. The term Human Development Index (HDI) has been developed in an effort to address these disparities. The HDI is a summary measure of average achievement in key dimensions of human development: a long and healthy life, being knowledgeable, and having a decent standard of living. The HDI is the geometric mean of normalized indices for each of the three dimensions.
The SDI, developed by GBD researchers, is a summary measure of development that uses lag-distributed income per person, average educational attainment in the population over age 15 years, and the total fertility rate. The SDI correlates reasonably well with HDI and is easy to obtain.
Approximately 85% of the world’s population live in LMICs. Recognizing that birth rates in a region are inversely related to income and human development, it can be estimated that more than 90% of the world’s children with CHD are born in LMICs. Although CHD is unlikely to be perceived as a pediatric health priority in regions with relatively high infant mortality rates (IMRs), it is increasingly important as the IMR declines. A declining trend in IMR is now being witnessed in almost every part of the world except for regions that are affected by armed conflict. This decline is almost entirely attributable to reductions in mortality from communicable diseases. Congenital heart defects have begun to surface as a significant health problem among infants and newborns in several regions that are now witnessing rapid and substantial improvements in human development indices.
Notwithstanding the decline in communicable diseases, RHD is still quite prevalent in LMICs, particularly among the poorest and marginalized sections of the populations that are often left isolated by dysfunctional health systems. Most LMICs have large pockets of poor and marginalized populations that include the rural poor, migrant laborers, and their families and residents of urban slums. Other acquired childhood heart diseases such as Kawasaki disease and myocarditis and cardiomyopathy are also likely to be substantial problems in terms of absolute numbers in LMICs as a whole.
Perhaps as a consequence of the demographic transition in pediatric heart disease, pediatric heart care has started to develop as a distinct entity in many LMICs in the past 30 years. It is growing rapidly in terms of number of new programs, caregivers, and patient numbers. Given the projections for the next 20 to 50 years in terms of economic growth and human development, it is likely that much of the global activity in terms of pediatric heart care will shift to the current LMICs.
However, there are several challenges in delivering pediatric heart care in terms of human and material resources, infrastructure, and deficiencies in systems of health care delivery in almost all LMICs. Socioeconomic issues such as poverty, ignorance, and limitations in primary health care alter the demography of the patient population, thereby presenting additional therapeutic challenges.
Health System Challenges in Low- and Middle-Income Countries
Comprehensive pediatric heart care requires the presence of a robust pediatric heart program that is supported by effective health systems. Box 88.1 lists the essential requirements for developing a successful comprehensive pediatric cardiac service. The first six requirements relate to specific attributes of the program, and the last four requirements relate to health systems in the region. Pediatric cardiac programs cannot function in isolation. Their effectiveness is closely linked to the health care environment of the region they serve.
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Robust infrastructure
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Quality equipment
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High level of skill among caregivers
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Cohesive teamwork
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Supportive administration
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Sustainable systems and services: education and training
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Easy geographic access
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Well-developed and mature referral base
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Favorable economics and human development in the region
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A system for charitable care
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Ethical practice environment that is not totally profit driven
Health System Challenges in Congenital Heart Disease Care
A number of health system challenges in LMICs come in the way of delivery of comprehensive pediatric heart care to every child born with CHD. These are listed in Table 88.1 . Dysfunctions in primary health care translate into deficiencies in antenatal care. Prenatal diagnosis of CHD is now well established in many advanced nations, where a substantial proportion of newborns with critical CHD are identified before birth. This enables termination of pregnancies in some of the fetuses with critical CHD when detection is before the legal limit for abortion. For many other fetuses with CHD, directed delivery at centers with facilities for comprehensive pediatric heart care is facilitated. This largely eliminates the challenges of having to transport newborns with critical CHD. In most LMICs, prenatal diagnosis of CHD is exceptional and largely limited to small populations around selected pediatric cardiac centers that have a well-developed fetal cardiology service. When one considers the fact that a country like India has approximately 26 million births every year, it is easy to understand that universal antenatal screening is practically impossible.
| Category | Specific Health System Challenges |
|---|---|
| Detection of CHD |
|
| Referral to pediatric heart program |
|
| Transport |
|
| Treatment |
|
Even in advanced nations with well-developed systems for perinatal care, there is potential for a number of critical CHDs to be missed at birth unless specific CHD screening programs are instituted. This is because symptoms and signs are uncommon in many newborns with CHD in the first 48 hours after birth. Newborn pulse oximeter screening is not mandated and therefore often not undertaken in most LMIC health care settings. Furthermore, a number of deliveries continue to happen at home and are largely unsupervised. Newborn screening is largely impossible in these circumstances. Even in the deliveries that happen under medical supervision in hospitals, CHD tends to be missed because of limited awareness among the health care personnel, including pediatricians. Because of the extraordinary paucity of pediatric heart programs in institutions with postgraduate training (residency) programs in pediatrics, most pediatric residents have little or no exposure to pediatric cardiology in their formative years. In the event CHD is suspected, facilities for accurate diagnosis in the form of echocardiography machines with pediatric and newborn transducers and skilled personnel are quite limited. It is also not uncommon for echocardiograms to be performed by adult cardiologists. As a result, erroneous reports are common.
There are many barriers to the timely referral of patients to a pediatric heart program even when CHD is suspected or recognized. Primary caregivers, including pediatricians, may not often perceive the urgency in referring of many critical CHDs. There is also a general perception that treating CHD is a futile exercise, contributing to failure of timely referral. Geographic barriers result from a severe shortfall of comprehensive pediatric heart programs in LMICs. Most programs are largely clustered in and around large cities. Geographic barriers in combination with poverty and ignorance conspire to ensure that most newborns with heart disease are not referred in a timely fashion. This is particularly true for most of Africa, large parts of eastern and northern India, Afghanistan, Pakistan, Iraq, and the central Asian countries. In some countries, such as India and China, there is gender bias favoring boys, and this is a significant barrier to girls with CHD getting attention.
Because there are no organized systems for transporting a sick newborn or infant with heart disease in LMIC settings, many neonates with CHD develop sepsis and end-organ injury prior to reaching a pediatric cardiac program. This significantly impacts mortality and morbidity. The vast distances that need to be covered to reach a pediatric heart program further compound these challenges. In addition, ambulance services (road or air) for newborn transport are expensive and generally beyond the reach of most families in LMICs. For newborns with critical CHD, reaching a tertiary care center while in circulatory collapse poses not only medical challenges but also ethical challenges when there is evidence of major neurologic insult.
The present combined capacity of all pediatric heart programs in LMICs falls woefully short of the actual requirements. Most programs are overwhelmed. Programs that provide care at subsidized costs often have long waiting lists of several thousand patients. Programs in private hospitals are expensive and unaffordable for the average family. Nevertheless, even these units are facing the pressure of increasing numbers of patients with financial means, as well as demand from overseas patients seeking better pediatric cardiac care.
Acquired Heart Diseases
Children with acquired heart disease have similar needs for their care as CHD in terms of infrastructure and resources.
Rheumatic Heart Disease (See Also Chapters 54 and 55 ).
RHD is largely a disease of the poor, underprivileged, and marginalized populations who often escape the gambit of health services, particularly when it is privatized. A detailed discussion on the burden of RHD is provided in Chapter 89 . Chapter 55 describes the epidemiology of RHD. Treatment of established RHD can be effectively undertaken only in comprehensive pediatric cardiac facilities and a shortfall in programs and personnel is likely to affect the quality of care and outcomes.
Kawasaki Disease (See Also Chapter 53 ).
Kawasaki disease is likely to be underreported in LMIC settings because it is likely to be unrecognized. Given the need for close clinical monitoring, advanced imaging, and expensive medications, health system deficiencies are likely to adversely impact children with Kawasaki disease in LMICs. Delays in administration of intravenous immunoglobulin are likely to translate into a higher incidence of coronary aneurysms and related complications.
Myocarditis and Cardiomyopathy (See Also Chapters 61 and 63 ).
The fundamental requirement of pediatric intensive care services for care of patients with advanced heart failure is in very short supply in LMICs. Advanced life support systems such as extracorporeal membrane oxygenation and ventricular assist devices are extremely scarce and largely unaffordable. Pediatric heart transplant is not a viable option in most LMICs because of virtual absence of organ donation networks and limitations in infrastructure and expertise. Furthermore, the cumulative costs of managing a patient with cardiac transplant is simply too prohibitive for the fragile health systems.
Patient Profile of Congenital Heart Disease in Low- and Middle-Income Countries
The patient profile of CHD that is typically seen in LMICs is unique because of the previously listed factors that contribute to late presentation. In addition, common childhood conditions that prominently include undernutrition and respiratory infections frequently complicate the clinical presentation of CHD. This section will discuss these specific challenges and suggest ways to approach them.
Late Presentation
Delays in presentation result in varied manifestations depending on the age and specific condition.
Critical Heart Diseases in Neonates.
Neonates with critical heart disease are especially vulnerable to delays in diagnosis and referral. In addition, they are also particularly vulnerable to clinical deterioration during transport. In absence of routine screening and because of limitations in supervision, CHD is often not diagnosed while the newborn is in hospital for the 24 to 48 hours following delivery. Critical CHD is often identified after discharge, when physiologic perturbations are clinically manifest. The newborn is typically brought back to a hospital following discharge, with varying degrees of insult in the form of hypoxia, end-organ injury, and/or metabolic derangement. In addition, the clinical picture is often further complicated by the common occurrence of neonatal sepsis with an increasing and alarming trend toward multidrug resistant bacterial and fungal infections. Although it is likely that a substantial number of newborns with CHD do not survive, the actual proportion of newborns who die because of untreated CHD has not been determined in the LMIC environment. Among survivors, neurologic insult is likely and a wide spectrum of possibilities ranging from subclinical insult to overt manifestations of hypoxic ischemic encephalopathy can occur. Given the fact that late diagnosis of CHD is not uncommon even in advanced nations with mature and well-resourced health systems. In LMICs many more newborns with CHD present are late when care is complicated and frequently no longer possible. The exact consequences that would result from late presentation vary depending on the specific CHD. Table 88.2 lists these consequences in the common CHD categories in the newborn.
| Congenital Heart Defect | Specific Consequences of Late Presentation |
|---|---|
| Transposition with intact ventricular septum | Regression of left ventricular mass that may preclude a successful arterial switch or increase risk of mortality and morbidity; Hypoxic injury to brain and other end-organs |
| Transposition with ventricular septal defect | Development of pulmonary vascular obstructive disease; Undesirable dilation of the neoaortic root, refractory pneumonia |
| Obstructed total anomalous pulmonary venous return | Delayed postoperative recovery from pulmonary congestion, pulmonary hypertensive crisis in the postoperative period, ventricular dysfunction |
| Duct dependent systemic circulation | Widespread organ dysfunction from hypoperfusion: Renal failure, seizures, liver dysfunction, necrotizing enterocolitis, and bloodstream sepsis |
| Duct dependent pulmonary circulation | Prolonged hypoxemia with attendant consequences as above |
The late presenting infant with transposition of great arteries is unique to LMICs, and the management of the regressed left ventricle in this situation has been the focus of much debate. The options vary from attempts at retraining the left ventricle prior to an arterial switch to supporting the left ventricle with mechanical support after a delayed primary arterial switch. Either option involves significant resource utilization and the need for great expertise in perioperative management for optimal outcomes. Given the paucity of availability of both resources and expertise in most places, the atrial switch operation (Senning procedure), which may be easier to perform and has more predictable early outcomes, is also an option for the late-presenting transposition with intact ventricular septum in LMICs.
Pulmonary Hypertension in Shunt Lesions.
In advanced nations, the widespread availability of heart surgery in the infant has largely eliminated the problem of children with left-to-right shunts presenting late with pulmonary hypertension. Typically, these lesions are “posttricuspid” shunts (these lesions are large VSDs and PDAs). However, in LMICs the vast majority of infants with large shunts are left unoperated because of limitations in access to infant heart surgery. There is also a prevailing misconception among many pediatricians that most septal defects are likely to close with time. This results in premature death among many infants who often succumb to heart failure and refractory pneumonia. Among survivors, a wide clinical spectrum of possibilities can be seen that is largely determined by the degree of elevation in pulmonary vascular resistance (PVR). At one end of the spectrum are children who are fortunate enough to remain operable with minimal elevations in PVR. At the other end are patients with frank Eisenmenger syndrome with shunt reversal and hypoxemia resulting from severe irreversible elevation in PVR ( Fig. 88.1 ). Included in this spectrum are patients who are often labeled as “borderline.” They present an important challenge in decision-making regarding operability. The available guidelines are largely based on expert consensus that is not yet substantiated by evidence from appropriately designed prospective studies. There are no clearly defined thresholds for PVR, ratios of pulmonary and systemic vascular resistance, and response to selective pulmonary vasodilators that consistently separate the “operable” from “inoperable.” This is because there are inherent limitations in accuracy of data obtained through cardiac catheterization.
A holistic approach that integrates clinical, noninvasive, and invasive data is often used to make a decision in this challenging group of patients. Surgical strategies in such patients have involved the use of fenestrated or valved patches to close the atrial or ventricular defects that would allow decompression of the right heart in the event of a postoperative pulmonary hypertensive crises. Selective pulmonary vasodilators, typically endothelin receptor antagonists (bosentan or ambrisentan) and phosphodiesterase inhibitors (sildenafil and tadalafil), are used for variable periods before and after surgery in these situations. However, there is no conclusive proof whether the strategy of “repair and treat or treat and repair” results in a sustained fall in PVR. An additional consideration is the altitude of their residence. A borderline case at sea level may not be operable if they return home to 4000 m.
Children with cyanotic heart disease and increased pulmonary blood flow (such as persistent truncus arteriosus or transposition with a large VSD or large patent arterial duct) have rapid and more predictable onset of elevation in PVR and tend to become inoperable at a relatively early age. Children with a functionally univentricular heart along with increased pulmonary blood flow often miss their opportunity to get a Fontan operation because the initial palliation (typically a pulmonary arterial band) is delayed considerably. Delays in surgery for complex CHD are particularly common because these operations are expensive and few centers have the capability to deal with them.
Consequences of Long-Standing and Severe Hypoxemia
Neurologic and neurodevelopmental consequences.
Children with CHD and the potential for right-to-left shunting experience a variety of adverse consequences that result from long-standing hypoxemia. Overt neurologic complications are common in the form of strokes due to paradoxical embolus or severe polycythemia. Severe neurologic insult can result from transient intense hypoxemia such as during a cyanotic “spell” ( Fig. 88.2 ). Iron deficiency anemia predisposes to occurrence of cerebral infarctions presumably by altering the rheology of red blood cells. These cells aggregate and clog the microcirculation of the brain.
Right-to-left shunts that bypass the pulmonary circulation constitute a substrate for cerebral abscess (see Fig. 88.2 ). This problem has largely disappeared in economically advanced nations because it is rare for children with cyanotic heart disease to remain unaddressed beyond 3 to 4 years of life. However, it is quite common for children in LMICs with cyanotic heart defects to remain unoperated in childhood, and brain abscess is therefore not uncommon. Severe hypoxemia and elevated hematocrit are associated with a high likelihood of development of brain abscess. It is widely recognized that long-standing hypoxemia and polycythemia are associated with a variety of adverse neurodevelopmental consequences.
Cardiac consequences of long-standing hypoxemia.
Both systolic and diastolic functions worsen with long-standing hypoxemia in children with cyanotic disease, and this adversely impacts postoperative recovery. Histologic studies of myocardial biopsy specimens obtained during surgical repair have shown that preexisting cardiomyocyte injury accompanied by mitochondrial damage and fibrosis is found to be more pronounced in older patients with tetralogy of Fallot and long-standing hypoxemia compared with those with less hypoxemia and/or of shorter duration. Patients with a functional univentricular heart and long-standing hypoxemia tend to have unacceptable elevations in end-diastolic pressures that sometimes preclude Fontan completion. The suggested underlying mechanisms of impaired ventricular performance include impaired free fatty acid metabolism, a high prevalence of cardiomyocyte apoptosis, and reduced myocardial adenosine triphosphate levels in the myocytes.
Patients with severe long-standing hypoxemia may demonstrate severely diminished ventricular function that may complicate decision-making because it is not often clear how much of the dysfunction would reverse after correction of hypoxemia. In some of these patients it may be necessary to perform a palliative procedure to improve oxygen saturation, allowing for recovery of ventricular function prior to corrective surgery. For example, in adults with uncorrected tetralogy of Fallot, it is sometimes necessary to undertake a palliative balloon pulmonary valvotomy to facilitate recovery of impaired left ventricular function. Likewise a bidirectional cavopulmonary shunt may help to reverse ventricular dysfunction in patients with a functionally univentricular heart and long-standing hypoxemia.
Effect of hypoxemia and erythrocytosis on other organ systems.
Hypoxemia and the attendant secondary erythrocytosis affect multiple organ systems ( Table 88.3 ) that may get overlooked in a busy clinical setting. As patients with cyanotic CHD get older, the effects of erythrocytosis dominate the clinical picture and account for most of the patients’ symptoms.
| Pathophysiologic Derangement | Manifestations |
|---|---|
| Secondary erythrocytosis | Hyperviscosity symptoms, relative iron, folic acid and vitamin B 12 deficiency, hyperuricemia, and gout |
| Bleeding diathesis | Hemoptysis, cerebral hemorrhage, menorrhagia, epistaxis |
| Altered red cell rheology and thrombotic diathesis | Cerebrovascular accidents (stroke or transient ischemic attacks), intrapulmonary thrombosis, and elevated pulmonary vascular resistance |
| Renal dysfunction | Glomerular abnormalities, hyperuricemia, and gout |
| Hepatobiliary dysfunction | Calcium bilirubinate gallstones, cholecystitis |
| Infections | Endocarditis, cerebral abscess, pulmonary tuberculosis |
| Skeletal disease | Scoliosis and hypertrophic osteoarthropathy |
Adverse Effects of Long-Standing Volume and Pressure Overload.
Uncorrected CHD with chronic pressure or volume overload results in varying degrees of irreversible changes that contribute to residual problems that persist after surgical correction. Volume overload can result from left-to-right shunts that occasionally persist for many years without significant elevation in PVR. Chronic ventricular enlargement predisposes to heart failure from ventricular dysfunction and, sometimes, atrioventricular valve regurgitation. The picture is often complicated by atrial enlargement with resultant atrial flutter and fibrillation. Severe ventricular hypertrophy results from uncorrected outflow obstructions and is often associated with residual dysfunction after relief of the obstruction because of myocardial fibrosis.
Undernutrition and Its Impact on Congenital Heart Disease
There is a significant burden of childhood undernutrition in low- and middle-income nations. The coexistence of CHD greatly increases the likelihood and severity of undernutrition, and this adds significantly to the existing challenges that include resource constraints, late presentation, and perioperative infection. In the initial publication of 15,049 patients with CHD from the International Quality Improvement Collaborative (IQIC), more than half the children were severely undernourished (weight z -scores of −3 or less) and 12% had an emaciated appearance prior to their surgery ( Fig. 88.3 ).
