Author + information
- Received February 13, 2017
- Revision received March 30, 2017
- Accepted April 13, 2017
- Published online December 4, 2017.
- Rafik Tadros, MD, PhDa,b,
- Eline A. Nannenberg, MD, PhDc,
- Krystien V. Lieve, MDa,
- Doris Škorić-Milosavljević, MDa,
- Najim Lahrouchi, MDa,
- Ronald H. Lekanne Deprez, PhDc,
- Jeroen Vendrik, MDa,
- Yolan J. Reckman, MDa,
- Pieter G. Postema, MD, PhDa,
- Ahmad S. Amin, MD, PhDa,
- Connie R. Bezzina, PhDa,
- Arthur A.M. Wilde, MD, PhDa,d and
- Hanno L. Tan, MD, PhDa,∗ ()
- aHeart Center, Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, the Netherlands
- bCardiovascular Genetics Center, Department of Medicine, Montreal Heart Institute and Université de Montréal, Montreal, Quebec, Canada
- cDepartment of Clinical Genetics, Academic Medical Center, Amsterdam, the Netherlands
- dPrincess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, Kingdom of Saudi Arabia
- ↵∗Address for correspondence:
Dr. Hanno L. Tan, Department of Cardiology and Laboratory of Clinical and Experimental Cardiology, Heart Center, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
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.
Drs. Amin, Bezzina, Wilde, and Tan have received support from the Netherlands CardioVascular Research Initiative, the Dutch Heart Foundation, the Dutch Federation of University Medical Centres, the Netherlands Organisation for Health Research and Development, and the Royal Netherlands Academy of Sciences (CVON PREDICT project CVON2012–10). Dr. Tadros has received support from the Canadian Heart Rhythm Society George Mines Award, the Montreal Heart Institute Foundation, and the Philippa and Marvin Carsley Cardiology Chair. Dr. Wilde is a member of the scientific advisory board of LivaNova. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page.
- Received February 13, 2017.
- Revision received March 30, 2017.
- Accepted April 13, 2017.
- 2017 American College of Cardiology Foundation