Clinical manifestations

Presentation and course

Table 1. Clinical Manifestations of Congenital Heart Disease

Prognosis and complications

Up to 25% of children with congenital heart disease experience neurologic complications (26). Neonates with congenital heart disease demonstrate different neurobehavioral performance (attention, regulation, asymmetry, increased nonoptimal reflexes, lethargy, and need for handling) than typically developing neonates (18). Eighty-five percent of infants born with congenital heart disease reach adulthood (43). A meta-analysis done in 2012 estimates that the prevalence of congenital heart disease in the adult population is 3,000 per million (44). Infants with congenital heart disease have alterations in brain size at 3 months of age; however, their brain growth is similar to that of healthy term infants. The primary predictor of brain growth in the congenital heart disease population is somatic growth, which highlights the importance of optimal weight gain (35). Von Rhein and colleagues studied structural brain lesions and neurocognitive impairment in adolescents with congenital heart diseases who underwent cardiac surgery (45). In this study, 21% of the patients in the population had white matter abnormalities and volume loss on MRI most consistent with a hypoxic-ischemic brain injury. Although none of the patients in the study had cerebral palsy, 34% of the patients had mild to moderate motor deficits. Additionally, total mean IQ was lower in the studied population than in the control; the patients with congenital heart disease had an IQ score of 105 +/- 15.8 whereas the control population had an IQ score of 113 +/-10.4 p = 0.009. Also, patients with congenital heart disease and brain lesions scored significantly lower in all assessed neurodevelopmental domains, especially motor performance, visual perception, and visuomotor integration when compared to those patients with congenital heart disease and no brain lesions. A study by The Colorado Congenital Heart Disease Surveillance System (COCHD) to investigate the prevalence of mental health illness among adolescents and adults with congenital heart disease revealed that 33% of adults and 20% of adolescents with congenital heart disease are affected by mental illness. Anxiety and mood disorders were greater than three times more likely in patients with severe congenital heart disease (requiring at least two cardiac procedures) compared to patients with simple congenital heart disease. Overall, developmental disorder was the most common mental illness diagnosis affecting adolescents, whereas adults with congenital heart disease are at increased risk of heart failure and atrial arrhythmias, which are associated with worse executive function, cognitive impairments, and dementia (21).

Clinical vignette

Case 1. During her 20^th week of pregnancy, a 33-year-old woman obtained a fetal ultrasound that showed a congenital heart malformation with suspected tetralogy of Fallot. Genetic evaluation revealed a deletion in the q11.2 region of 1 chromosome of the pair of chromosomes 22, consistent with DiGeorge syndrome. A child born with a ventricular septal defect was confirmed via echocardiography to have tetralogy of Fallot. Three days following uncomplicated vaginal vertex delivery, the neonate presented a sudden onset of weakness of the right arm and lower right side of the face, cortical thumbing, and persistent fisting. Deep tendon reflexes were decreased in the right biceps and right patella. On day 4 of life, the child exhibited episodic posturing of the right arm, with tonic extension and clonic activity (29).

A CT scan of the child’s head showed a hypodense, wedge-shaped region in the left middle cerebral artery distribution. There was no incidence of hemorrhage. An EEG obtained in the neonatal intensive care unit demonstrated decreased amplitude over the left hemisphere. Spike-wave discharges were noted over the left central region. MRA revealed thrombotic occlusion of the left middle cerebral artery. Following these tests, phenobarbital was administered.

Case 2. A 2020 case report by Lakhani and colleagues describes the case of a 13-year-old boy with known uncorrected tetralogy of Fallot (TOF) who presented to a cardiac center in Pakistan with shortness of breath, high-grave fever, headache, and two episodes of generalized tonic-clonic seizures with altered consciousness for three days (24). On general physical examination he was alert and oriented with no focal neurologic deficits. There was digital clubbing and cyanosis, with varying oxygen saturation from 85% to 90%. Infective endocarditis was suspected, but there were no peripheral signs. Cardiac examination revealed a displaced PMI to the left 5th intercostal space within the midclavicular line, left parasternal heave, and a harsh systolic ejection murmur of grade III/VI audible at the left sternal border and accentuated with inspiration. Labs were significant for polycythemia (hematocrit of 44.7%), leukocytosis with a neutrophilic predominance, and a positive blood culture for Escherichia coli. Echocardiogram revealed all components of uncorrected TOF with no evidence of endocarditis. CT scan of the brain confirmed diagnosis of brain abscess with a small, well-defined, ring-enhancing hypodense lesion in the right parieto-occipital region with surrounding edema. He was managed conservatively with intravenous antibiotics (vancomycin and meropenem), acetaminophen, and anticonvulsant (sodium valproate) for two weeks. Repeat imaging showed regression of in size of abscess, and repeat blood culture showed no growth. He was discharged home on two weeks of oral antibiotics (cefotaxime and metronidazole).

Biological basis

Etiology and pathogenesis

Congenital heart disease can be caused by a number of factors ranging from inherited genetic mutations or spontaneous mutations to environmental factors. The most common genetic factors that lead to heart abnormalities are outlined in Table 2 (17):

Table 2. Genetic Factors Leading to Heart Abnormalities

Congenital heart disease may be caused by Mendelian mutations, de novo mutations, noncoding mutations, copy number variants (SNV), translocations, or single nucleotide polymorphisms (SNP) (23; 16). There are two paradigms that attempt to explain the various mutations that lead to congenital heart disease. The direct convergence model theorizes that different risk factors impact the same genes and molecules. In the functional convergence model, congenital heart disease is caused by various risk factors, both genetic and environmental, that affect various molecules involved in a network of heart development. Through studies conducted on both human and animal models, Lage and colleagues discovered that the functional convergence model best explains the development of congenital heart disease. The researchers concluded that there was a lack of direct convergence between risk and responder datasets; more interestingly, however, they discovered functional convergence between thousands of risk factors. Although the genetic and environmental factors that cause congenital heart disease participate in many molecular pathways, they participate in a larger protein interaction network that drives the development of cardiac structures (23). At this time, we look forward to the results of functional genomic studies using single-cell RNA-sequencing, ChIP-sequencing, and ATAC-sequencing to reveal complex intrinsic genetic networks with specific cardiac lineages in early heart development (14).

Environmental factors include the following (06; 17; 42):

Table 3. Environmental Factors Leading to Heart Abnormalities

The most common heart defects associated with congenital heart disease are outlined in Table 4 (American Heart Association):

Table 4. Heart Defects Most Commonly Found in Congenital Heart Disease Patients

Of these heart defects, some are more likely to cause neurologic complications than others. The incidence of neurologic abnormalities in various types of congenital heart disease is outlined in Table 5 (31):

Table 5. Incidence of Neurologic Abnormalities Associated with Specific Congenital Heart Defects

The heart defects mentioned above can be divided into three categories: (1) left-to-right shunts, (2) obstructive lesions, and (3) those defects that cause cyanotic heart disease.

Each of the three categories and certain caveats are further outlined in Tables 6, 7, and 8. In addition, the pathogenesis and pathophysiology are included (31).

Table 6. Neurologic Impairments Associated with Left-to-Right Shunts

Table 7. Neurologic Impairments Associated with Obstructive Lesions

Table 8. Neurologic Impairments Associated with Cyanotic Congenital Heart Disease

Epidemiology

In 2003, more than 25,000 cardiovascular operations for congenital cardiovascular defects were performed on children younger than 20 years of age (40). Cardiothoracic surgeons began operating on infants with congenital heart disease about 50 years ago, and since then mortality of this population has improved from 95% to 5% (09). Inpatient mortality rate after all types of cardiac surgery was 4.8%. Mortality risk varies for different defect types (08). The prevalence of congenital heart disease in the adult population is 3000 per million (44). The types of surgeries to correct congenital heart defects are outlined in Table 9 (33). Table 10 describes the prevention of congenital heart disease.

Table 9. Surgery to Correct Congenital Heart Defects

Prevention

Table 10. Prevention of Congenital Heart Disease

Differential diagnosis

The clinical signs of a focal neurologic deficit or altered mental status with or without seizures will lead the astute clinician immediately to a workup for stroke, abscess, or hemorrhage in a patient with congenital heart disease. Certain illnesses may masquerade as stroke, hemorrhage, or abscess, and should be noted (Table 11).

Table 11. Common Illnesses That Masquerade As Stroke, Hemorrhage, or Abscess

In the younger pediatric age group, certain illnesses appear to have central nervous system origin and may occur in congenital heart disease patients (Table 12) (27).

Table 12. Illnesses of CNS Origin That Most Commonly Occur In Congenital Heart Disease

Common illnesses of CNS origin

Diagnostic workup

Congenital heart disease is usually not detected well with routine newborn examination, mostly because babies with congenital heart disease do not show signs of their disease at the exam. Although there has been much debate and discussion on using pulse oximetry to detect or screen for cyanotic heart disease (especially transposition of the great arteries, TGA), data suggest that even newborns with TGA can have O2 saturation levels higher than 96%, making this a very impractical screening mechanism (37).

In children confirmed to have congenital heart disease via echocardiography and electrocardiography, testing should be done to evaluate potential neurologic complications (19). Additional diagnostic tools are displayed in Table 13.

Table 13. Diagnostic Tools to Evaluate Neurologic Impairments in Congenital Heart Disease Patients

Based on the results of these studies, the workup for stroke and other diseases in the differential of stroke can be planned (07). MRA is a noninvasive method of visualizing the intracranial vasculature, and although conventional angiography is still the “gold standard,” MRA can largely replace invasive methods in the evaluation of ill children.

Table 14. ICD Codes Applicable for Neurologic Complications of Congenital Heart Disease [In Progress]

Management

Arrhythmia is the main reason for the hospitalization of adults with congenital heart disease and is an increasingly frequent cause of morbidity and mortality. Due to the additive effects of hypoxia, patients with congenital heart disease are susceptible to malnutrition and growth failure. Cyanotic patients with pulmonary hypertension are most severely affected (32). Care must be given to the nutritional needs of these children.

Because patients with cyanotic congenital heart disease are at a greater risk of cerebrovascular accident resulting from iron deficiency, administration of one tablet of ferrous sulfate (or gluconate) is recommended. Hemoglobin should be rechecked within 7 to 10 days. If red cell count is drastically increased, iron should be discontinued (12).

Outcomes

Table 15. Nonsurgical complications

Phrenic nerve injury also may occur in 5% of congenital heart disease repairs (32).

Table 16. Neurologic complications from cardiac surgery

Given the high prevalence of cerebral desaturation during corrective cardiac surgeries, postoperative neurologic complications have been investigated with use of cerebral oximetry (intervention to monitor and correct desaturation). Although there are no significant differences observed for postoperative delirium and postoperative strokes, cerebral oximetry was associated with a lower incidence of postoperative cognitive decline up to three months after cardiac surgery when compared with control (no cerebral oximetry) (10).

Special considerations

Pregnancy

The benefits and risks of contraception and pregnancy in females diagnosed with congenital heart disease should be discussed with specialists in adult congenital heart disease and obstetrics and gynecology. There are certain types of contraceptives that can be hazardous to a woman’s health, causing thromboembolism or fluid retention (46). Postoperative females of childbearing age with corrected or uncorrected congenital heart defect should be aware of the hemodynamic burden of pregnancy that increases the risk of cardiovascular complications including strokes. Labor in the lateral decubitus position minimizes the hemodynamic fluctuations correlated with major uterine contractions in the supine position (01). Because thromboembolism is likely to increase during the postpartum period, patients with lesions susceptible to paradoxical embolization require meticulous leg care, use of elastic support stockings, and early ambulation (36).

Anesthesia

Medications used can have neuromuscular side effects, thereby mimicking neurologic events. Anesthetic medications should be included in the differential diagnosis of adverse events (04).