Ajmaline testing for early detection of Arrhythmogenic Cardiomyopathy (ACM)

Rationale: Arrhythmogenic Cardiomyopathy (ACM) is a disease with a genetic origin and involves cardiac desmosomes dysfunction and fibrofatty replacement of the myocardium. Clinically, patients present with ventricular arrhythmias or sudden cardiac death. Genetic testing in family members of patients with ACM shows incomplete penetrance of the disease. Earlier studies have shown that the electromechanical interval and RV deformation imaging is abnormal in the subtricuspid area of the right ventricle (RV) even in the early stage of disease. We hypothesize that ajmaline induces more pronounced electrical and mechanical dysfunction of those myocardial areas that are affected in the early stage of ACM. Therefore, this ajmaline provocation could identify those mutation carriers who are at risk for the development of ACM, arrhythmias and/or sudden cardiac death.



Objective: Describe the electrocardiographic changes and areas of late myocardial activation using electrocardiographic imaging in PLN and PKP2 mutation carriers during ajmaline provocation.



Study design: Multicentre, diagnostic trial, cohort study



Study population: All patients who are diagnosed with ACM due to an PLN and PKP2 mutation and their asymptomatic family members who are PKP2 and PLN mutation carriers known in the UMC Utrecht, UMC Groningen and Amsterdam Medical Centre. Patients with structural normal hearts (determined by echocardiography or cardiac MRI) who are referred for ajmaline provocation to exclude Brugada syndrome.



Intervention: ajmaline (class 1c sodium channel blocker, with a short half-life) infusion in fractions of 10mg every minute up to a target dose of 1mg/kg.



Main study parameters/endpoints: difference in mean activation time duration (ATD) of the subtricuspid area before and after ajmaline provocation using electrocardiographic imaging (ECGI).

Ajmaline induces more pronounced electrical and mechanical dysfunction of those myocardial areas that are affected in the early stage of ACM. Therefore, this ajmaline provocation and electrocardiographic imaging could identify those mutation carriers who are at risk for the development of ACM, arrhythmias and/or sudden cardiac death.

T0 selection

T1 ajmaline provocation

T2 bloedtest liver parameters

T3 Regular follow up

Ajmaline provocation