Pathophysiological Mechanisms, Clinical Spectrum, And Contemporary Strategies in the Diagnosis and Management of Brugada Syndrome: A Comprehensive Review

Brugada syndrome represents a complex and potentially life-threatening cardiac arrhythmogenic disorder characterized by distinctive electrocardiographic abnormalities and a uniquely elevated risk of sudden cardiac death in structurally normal hearts. Originating primarily from inherited ion channel dysfunctions, particularly involving sodium channelopathies, this syndrome has revolutionized the clinical understanding of ventricular arrhythmogenicity and electrophysiological heterogeneity. Its clinical manifestations are highly variable, ranging from asymptomatic incidental electrocardiographic findings to malignant arrhythmic events such as polymorphic ventricular tachycardia and ventricular fibrillation. The pathogenesis involves intricate interactions between electrophysiological substrates, genetic susceptibility, environmental triggers, and autonomic imbalance. Diagnostic evaluation has evolved substantially and incorporates high-resolution electrocardiography, provocative pharmacological testing, high-fidelity risk stratification, and advanced electrophysiological mapping. Despite remarkable technological and conceptual advances, the clinical approach remains challenging due to dynamic electrocardiographic patterns, unpredictable arrhythmic risk, and variable penetrance. Current therapeutic strategies emphasize prevention of sudden cardiac death through implantable cardioverter-defibrillator therapy in high-risk phenotypes and emerging targeted pharmacological and ablative interventions. The ongoing evolution in the understanding of molecular genetics, ion channel physiology, and arrhythmogenic substrates reinforces Brugada syndrome as a model disease for the study of primary electrical disorders of the heart. This review provides a comprehensive discussion of the epidemiology, underlying mechanisms, diagnostic paradigms, clinical presentation, and therapeutic approaches, emphasizing contemporary perspectives and future directions in the management of this increasingly recognized cardiovascular entity.