Serial ECG changes predict disease progression in Lev Syndrome: Implications for preventive pacemaker therapy

Abstract Background Lev syndrome represents a critical yet underdiagnosed cause of progressive cardiac conduction disorders that significantly increases mortality risk through sudden cardiac death. Its insidious progression from asymptomatic conduction delays to life-threatening complete heart block makes timely recognition essential for implementing life-saving interventions. Purpose To analyze the clinical presentation, electrocardiographic features, pathophysiology, and management approaches of Lev syndrome. Methods This retrospective analysis examined data from 127 patients (73 males, 54 females, mean age 64.3 years) diagnosed with Lev syndrome across multiple centers between 1990-2020. The study evaluated clinical presentations, ECG patterns, treatment outcomes, and available histopathological findings from cardiac tissue to characterize the syndrome's progression and response to interventions. Results Lev syndrome demonstrates age-dependent progression, with 87% of cases diagnosed after age 40. Initial ECG findings include first-degree AV block with left bundle branch block in 68% of cases, progressing to higher-grade blocks in 2-5 years. Serial ECGs frequently show a dynamic pattern of conduction abnormalities, with 42% of patients experiencing intermittent normalization of conduction between episodes of block. Pathological studies show fibrosis affecting the His bundle in 93% of specimens, and Purkinje fiber degeneration in 89%. Significant fibro-calcific changes of the cardiac skeleton are present in all cases, distinguishing it from Lenègre disease. Cardiomegaly is observed in 57% of patients, though ventricular function is typically preserved until late disease stages. Approximately 74% of patients experience syncope during disease progression, with 38% reporting associated parasympathetic symptoms. Emergency room presentations with bradycardia and altered mental status occur in 22% of initial diagnoses. Medical management with anticholinergic medications shows only transient benefit in 31% of cases. Permanent pacemaker implantation prevents Stokes-Adams attacks in 94% of treated patients, with 5-year survival improving from 37% in untreated patients to 82% in pacemaker recipients. Pacing dependency occurs in 76% of patients within 3 years of implantation. Mortality remains highest during the transition from intermittent to permanent complete heart block, with sudden cardiac death occurring in 23% of undiagnosed cases. Conclusion Lev syndrome represents an important differential diagnosis for adult-onset conduction abnormalities. Early recognition is critical as the condition is progressive and may result in fatal bradyarrhythmias. Permanent pacemaker implantation remains the cornerstone of treatment, significantly improving prognosis and quality of life in affected individuals.