This article series addresses high-risk but uncommon diseases encountered in the emergency department (ED). Each article in this series defines the disease or clinical presentation to be reviewed, provides an overview of our current understanding, and discusses pearls and pitfalls in the care of these patients using a question-and-answer format.

This sub-series of articles will address the “catastrophic neonate,” or disease states that cause a neonate to present to the ED in extremis, requiring prompt stabilization, diagnosis, expert consultation, and coordination of transfer to specialized centers. This article will discuss congenital heart disease (CHD) with a high likelihood of presenting with cyanosis, also referred to as critical or cyanotic CHD (CCHD). Acyanotic congenital heart disease will be discussed in a separate article [1].

Consisting of 12 phenotypes or defects, CCHD is here defined as a congenital cardiac defect presenting with hypoxemia [1]. This article will discuss the most common types of CCHD: truncus arteriosus, dextro-transposition of the great arteries (d-TGA), tricuspid atresia, tetralogy of Fallot (TOF), and total anomalous pulmonary venous return (TAPVR), often referred to as the 5 Ts, as well as severe Ebstein's anomaly, critical pulmonary stenosis, and hypoplastic left heart syndrome (HLHS). The anatomical defects that characterize each of these are outlined in Table 1.

Cyanosis due to congenital heart disease usually occurs when deoxygenated blood enters the systemic circulation, leading to blue discoloration of the skin and mucous membranes. The pathophysiology of CCHD can be categorized into two groups: lesions with inadequate or ineffective pulmonary blood flow and those with increased pulmonary blood flow [[2], [3], [4]]. The blood flow leading to cyanosis particular to each defect are described in more detail in Table 1.

Lesions with inadequate pulmonary blood flow are characterized by an obstruction of the pulmonary outflow tract and communication between the right and left sides of the heart, leading to right-to-left shunting and delivery of deoxygenated blood to the systemic circulation. The degree of cyanosis depends on the severity of the pulmonary outflow obstruction. When the obstruction is not severe, cyanosis may only occur in times of stress, leading to inadequate pulmonary blood flow, such as in the “hypercyanotic” spells characteristic of TOF. When the obstruction is severe, oxygenation is dependent on the patency of the ductus arteriosus; therefore, patients develop hypoxemia and shock when the patent ductus arteriosus (PDA) closes, generally within a few days or weeks of life. Lesions characterized by inadequate pulmonary blood flow include tricuspid atresia, TOF, critical pulmonary stenosis, and the various phenotypes of a single ventricle physiology [[2], [3], [4]].

Lesions with increased pulmonary blood flow present with cyanosis due to abnormal ventricular-arterial connections or significant mixing of systemic and pulmonary venous blood within the heart. These defects may depend on a PDA or patent foramen ovale (PFO) for mixing, such as in transposition of the great vessels. Significant mixing lesions within the CCHD group include defects with a common atrium or ventricle, TAPVR, and truncus arteriosus. Patients will have a combination of cyanosis and heart failure. However, if an obstruction is present, such as in pulmonary stenosis, neonates may present with cyanosis alone [[2], [3], [4]].

CCHD occurs in an estimated 2 per 1000 births [[5], [6], [7]]. While advances in prenatal ultrasound and newborn pulse oximetry screenings have improved early diagnosis, 25 % of neonates with CCHD remain undiagnosed upon hospital discharge [6]. There are over 46,000 ED visits per year for CHD [8], and patients presenting with CHD were nearly three times as likely to be under the age of 1. Furthermore, these infants are often critically ill at the time of presentation [7]. A 2025 retrospective cohort study of neonates with presenting with cardiovascular collapse found that 69 % had a structural heart defect, and nearly one third of these patients had a cyanotic defect [9]. CCHD remains a leading cause of mortality from birth defects, and delays in diagnosis, whether prenatally or postnatally, lead to significant morbidity and mortality [10].