Yield and Pitfalls of Ajmaline Testing in the Evaluation of Unexplained Cardiac Arrest and Sudden Unexplained Death: Single-Center Experience With 482 Families.

OBJECTIVES: This study evaluated the yield of ajmaline testing and assessed the occurrence of confounding responses in a large cohort of families with unexplained cardiac arrest (UCA) or sudden unexplained death (SUD). BACKGROUND: Ajmaline testing to diagnose Brugada syndrome (BrS) is routinely used in the evaluation of SUD and UCA, but its yield, limitations, and appropriate dosing have not been studied in a large cohort. METHODS: We assessed ajmaline test response and genetic testing results in 637 individuals from 482 families who underwent ajmaline testing for SUD or UCA. RESULTS: Overall, 89 individuals (14%) from 88 families (18%) had a positive ajmaline test result. SCN5A mutations were identified in 9 of 86 ajmaline-positive cases (10%). SCN5A mutation carriers had positive test results at significantly lower ajmaline doses than noncarriers (0.75 [range: 0.64 to 0.98] mg/kg vs. 1.03 [range: 0.95 to 1.14] mg/kg, respectively; p < 0.01). In 7 of 88 families (8%), it was concluded that the positive ajmaline response was a confounder, either in the presence of an alternative genetic diagnosis accounting for UCA/SUD (5 cases) or noncosegregation of positive ajmaline response and arrhythmia (2 cases). The rate of confounding responses was significantly higher in positive ajmaline responses obtained at >1 mg/kg than in those obtained at ≤1 mg/kg (7 of 48 vs. 0 of 41 individuals; Fisher's exact test: p = 0.014). CONCLUSIONS: In line with previous, smaller studies, a positive ajmaline response was observed in a large proportion of UCA/SUD families. Importantly, our data emphasize the potential for confounding possibly false-positive ajmaline responses in this population, particularly at high doses, which could possibly lead to a misdiagnosis. Clinicians should consider all alternative causes in UCA/SUD and avoid ajmaline doses >1 mg/kg.