Cyanotic Spells in Children with Tetralogy of Fallot: A Scoping Review

Background: Cyanotic or hypercyanotic spells are acute episodes of worsening cyanosis in children with Tetralogy of Fallot (TOF), potentially causing profound hypoxemia, neurological manifestations, and hemodynamic compromise. Evidence regarding their definition, pathophysiology, predictors, management, and outcomes remains heterogeneous and seldom analyzed. Aim: Our aim is to systematically map the evidence on cyanotic spells in pediatric patients with TOF, focusing on clinical presentation, precipitating factors, mechanisms, predictors, management, and outcomes. Methods: Under PRISMA-ScR guidelines for scoping review, we searched the PubMed/MEDLINE electronic database for English-language original manuscripts published up to August 2026, supplemented by reference-list screening. Original studies reporting extractable TOF-specific cyanotic-spell data in pediatric patients were eligible. Two reviewers independently screened records, and we descriptively synthesized the extracted data. Results: A total of 39 studies were included, comprising physiological investigations, case reports and series, observational cohorts, pharmacological studies, and catheter-based interventions. Heterogeneous terminology, definitions, clinical characterization, and outcome reporting were noted. Cyanotic spells were characterized by episodic worsening of cyanosis, often accompanied by hyperpnea and, in severe episodes, neurological manifestations. Available evidence suggests a potential interaction between right ventricular outflow tract (RVOT) anatomy and dynamic physiological factors. Conal septal geometry has been proposed as a potential anatomical marker, whereas available evidence suggests limited predictive value of peak Doppler RVOT gradient. Propranolol was the most extensively investigated pharmacological treatment strategy. More recent studies evaluated balloon-based interventions and RVOT stenting; selected reports described improved oxygenation and control or reduction of recurrent spells. Comparative and long-term evidence was limited. Conclusions: Cyanotic spells remain a potentially severe clinical manifestation in children with TOF. No validated predictive model is currently available, and only a limited number of candidate predictors have been directly evaluated. Standardized definitions and prospective studies integrating clinical, anatomical, echocardiographic, and physiological variables are needed to improve risk stratification and evaluate subsequent outcomes.