Unexplained Syncope & Response to Ajmaline in the Elderly

  • Giulio Conte
  • 28.05.20

Dr Giulio Conte
Cardiocentro Ticino, Lugano, Switzerland

Case Presentation

A 77-year-old male patient was referred to our institution because of recurrent syncopal events without prodromal symptoms. He had no family history of sudden cardiac death (SCD) and no history of chest pain, dyspnea or fatigue. Cardiological work-up including two-dimensional echocardiography, exercise stress test, tilt-table testing, and coronary angiography did not reveal any significant abnormalities. A 7 day electrocardiogram (ECG) monitoring did not show evidence of cardiac arrhythmias. Neurological evaluation and carotid artery duplex scan were normal. Baseline ECG showed sinus rhythm with 1st degree atrioventricular (AV) block (PR interval 220 ms) and atypical complete right bundle-branch-block (RBBB) with QRS duration of 125 ms and fragmentation in leads aVR, aVL and V1-V4 (Figure 1a). Furthermore, J waves with an amplitude of 1.5 mV were present in leads III and aVF.

Figure 1: Ajmaline challenge and HV measurement during EP study (before and after ajmaline administration).Source: G Conte 2020. Reproduced with permission from the author.  

Based on the clinical history and the presence of an inferior early repolarization pattern, an ajmaline challenge was deemed appropriate to rule out Brugada syndrome (BrS). Unexpectedly, inferior J waves amplitude increased during ajmaline infusion (1 mg/kg IV) and a coved-type Brugada type 1 ECG was unmasked in the inferior leads exclusively as indicated by the arrows in Figure 1a.


Which is the condition underlying these ECG findings and the mechanisms causing the syncopal events: BrS with uncommon phenotypic expression, concealed AV conduction disease or both? Would an electrophysiology study (EPS) be appropriate?


The diagnostic management of elderly patients with recurrent syncope and AV conduction disturbances can be challenging. The ajmaline challenge is an established tool to unmask BrS in patients with recurrent syncope, a structurally normal heart and non-diagnostic baseline ECG. In most cases of BrS, Brugada type 1 ECG is induced in the right precordial leads and very rarely, (up to 5 % of cases), in inferior and/or lateral leads only1, 2. These cases should be considered as having BrS.

Furthermore, European guidelines for the diagnosis and management of syncope3 recommend an EPS in patients with BBB (class IIa, level of evidence B), since abnormal His-ventricular (HV) interval measurement as well as development of intra- or infra-Hisian block on incremental atrial pacing are highly predictive of impending AV block4, 5. Additionally, in elderly patients with recurrent syncope and AV conduction abnormalities on baseline ECG, an ajmaline challenge during an EPS is valuable to rule-out BrS and assess intra- and infra-Hisian conduction6. Prolongation of the HV interval ≥ 100 ms during ajmaline infusion has been considered diagnostic for AV conduction disease7, 8. In these cases, pacemaker implantation is indicated.

In our case, baseline HV interval was normal (38 ms) and no intra or infra-Hisian block occurred during incremental atrial pacing. Corrected sinus node recovery time (400 ms) was also normal, excluding sinus node disease. In order to evaluate the arrhythmic origin of the syncopal episodes, programmed ventricular stimulation (PVS) was performed and no sustained ventricular arrhythmias (VA) were induced.

At the end of EPS, the ajmaline challenge was repeated and HV interval prolonged from 38 to 73 ms during drug administration as indicated by the arrows shown in Figure 1b.

Performing an EPS combined with an ajmaline challenge allowed us to exclude AV conduction disease and hence the necessity of pacemaker implantation. Furthermore, in accordance with the current guidelines,1 the patient did not qualify for ICD implantation, since the diagnosis of Brugada type 1 ECG appeared only after infusion of a class I antiarrhythmic drug and no VAs were induced during PVS. However, as reported by a recent pooled analysis on PVS in BrS, the annual incidence of spontaneous VAs in drug-induced BrS patients with syncope and no VA inducibility during PVS is not negligible (1.3% per year).9 Therefore, indication to ICD implantation was discussed and refused by the patient.

In patients with recurrent syncope, RBBB and signs of AV conduction disturbances, performing an ajmaline challenge during EPS is crucial to confirm BrS diagnosis and exclude AV conduction disease. However, the device-based management of these patients remains controversial.


1. Antzelevitch C, Yan GX, Ackerman MJ, et al. J-Wave syndromes expert consensus conference report: Emerging concepts and gaps in knowledge. Heart Rhythm 2016;10:e295-324.

2. Sarkozy A, Chierchia GB, Paparella G, et al. Inferior and lateral electrocardiographic repolarization abnormalities in Brugada syndrome. Circ Arrhythm Electrophysiol 2009 Apr;2(2):154-61.

3. Moya A, Sutton R, Ammirati F, et al. Guidelines for the diagnosis and management of syncope. Eur Heart J 2009;30(21):2631-71.

4. Scheinman MM, Peters RW, Suavé MJ, et al. Value of the H-Q interval in patients with bundle branch block and the role of prophylactic permanent pacing. Am J Cardiol 1982;50:1316–1322.

5. Dhingra RC, Wyndham C, Bauernfeind R, et al. Significance of block distal to the His bundle induced by atrial pacing in patients with chronic bifascicular block. Circulation 1979;60:1455–1464.

6. Conte G, Levinstein M, Sarkozy A, et al. The clinical impact of ajmaline challenge in elderly patients with suspected atrioventricular conduction disease. Int J Cardiol 2014;172(2):423–7.

7. Click RL, Gersh BJ, Sugrue DD, et al. Role of invasive electrophysiologic testing in patients with symptomatic bundle branch block. Am J Cardiol 1987;59:817–23.

8. Pentimalli F, Bacino L, Ghione M, et al. Ajmaline Challenge To Unmask Infrahisian Disease In Patients With Recurrent And Unexplained Syncope, Preserved Ejection Fraction, With Or Without Conduction Abnormalities On Surface ECG. J Atr Fibrialltion 2016;9(2):1421.

9. Sroubek J, Probst V, Mazzanti A, et al. Programmed Ventricular Stimulation for Risk Stratification in the Brugada Syndrome: A Pooled Analysis. Circulation 2016;133(7):622‐630. doi:10.1161/CIRCULATIONAHA.115.017885.