No registrations found.
ID
Source
Health condition
Arrhythmogenic cardiomyopathy, ARVC, carriers of pathogenic PLN and PKP2 mutations
Sponsors and support
Intervention
Outcome measures
Primary outcome
Mean changes in Activation Time Duration before and during ajmaline administration between the subtricuspid area and LV/RV/RVOT as calculated by ECG imaging.
Secondary outcome
Ventricular tachycardia, sudden cardiac death, ventricular fibrillation or development of arrhythmogenic cardiomyopathy (fulfilment of the Task Force Criteria) during follow up.
Electrocardiographic parameters (PQ, QRS and QTc intervals, the occurrence of the type I Brugada pattern, terminal activation duration) before, during and directly after ajmaline provocation.
Adverse events of ajmaline provocation
Background summary
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).
Study objective
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.
Study design
T0 selection
T1 ajmaline provocation
T2 bloedtest liver parameters
T3 Regular follow up
Intervention
Ajmaline provocation
R.W. Roudijk
Postbus 85500
Utrecht 3508 GA
The Netherlands
088-7568992
r.w.roudijk@umcutrecht.nl
R.W. Roudijk
Postbus 85500
Utrecht 3508 GA
The Netherlands
088-7568992
r.w.roudijk@umcutrecht.nl
Inclusion criteria
Patients or asymptomatic carriers of pathogenic PLN mutation, pathogenic PKP2 mutation or patients without structural heart disease who are referred for ajmaline provocation to exclude Brugada syndrome.
New York Heart Association functional class ¡Ü 1.
Exclusion criteria
Severe hepatic impairment (Child-Pugh class C)
Severe renal dysfunction (eGFR <30 ml/min/kg)
Symptomatic heart failure, NYHA ¡Ý 2
Women who are currently pregnant
Known intolerance or contraindication to Ajmaline
Sick sinus syndrome, second or third degree AV block without pacemaker implantation
Recent myocardial infarction
Known strong allergic reaction to ECG electrodes
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL6861 |
| NTR-old | NTR7039 |
| Other | EudraCT: 2018-000752-18 : METC nummer: 17-924, ABR nummer: 65196 |