Standard, high lead and sodium channel provoked electrocardiograms of a healthy volunteers will be performed to observe the various ECG changes. Participants will the undergo detailed imaging with cardiac magnetic resonance imaging and deep genotyping to identify structural or genetic variants which might dictate the electrocardiographic patterns at rest and with sodium channel provocation.
The investigators will recruit healthy subjects without a history of cardiac symptoms or a family history of sudden death or premature arrhythmogenic cardiac disease. Participants will undergo electrocardiographic phenotype assessment with standard and high lead electrocardiogram and sodium channel provocation. Detailed cardiac structural examination will be performed with cardiac magnetic resonance imaging to look for any variation in mainly right ventricular outflow tract structure and myocardial architecture. Participants will also undergo targeted genomic sequencing to look for variations in genes encoding for cardiac sodium channel.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
100
Ajmaline 1milligram/kilogram max dose as bolus intravenous over 10 minutes with continuous ECG monitoring
St George's University Of London
London, United Kingdom
The qualitative and quantitative effects of ajmaline provocation on parameters of cardiac conduction in healthy subjects using the surface electrocardiogram
The investigators will be undertaking quantitative analysis of the changes in cardiac conduction observed in the presence of ajmaline. This is measured in time intervals in milliseconds (ms) and magnitude of electrical conduction which will be expressed in millivolts (mv), but can also be expressed in millimetres (mm). The investigators will use the latter to quantify area changes which will be expressed as millimetres squared (mm2). A quantitive description of the electrocardiographic patterns observed will also be performed in addition to further qualitative analysis of vectors created by the variety of ECG morphologies observed, this geometrical assessment will be measured in degrees. As this is a cohort of healthy volunteers the variations observed are anticipated to be part of the "normal" variation, therefore the statistical analysis of these findings will be as a cohort not individual.
Time frame: ten minutes
The influence of normal variations in right ventricular outflow tract dimensions on the electrocardiographic response to ajmaline provocation in healthy subjects using cardiac magnetic resonance imaging.
Using existing cardiac magnetic resonance imaging modality, cardiac dimensions will be measured in millimetres (mm). This includes wall thickness and internal cavity size. Additionally volumetric assessment for chamber size will be made using millilitres (ml), this allows for a 3 dimensional appreciation. Using contrast agents, an assessment of the composition of cardiac muscle can be made and can identify the presence or absence of "myocardial fibrosis,"as a binary outcome measure. Further methods will be used to quantify the degree of fibrosis if observed, this will be expressed as a percentage (%) area of fibrosis divided by total area of myocardium multiplied by 100. The location of this fibrosis within the heart will also be noted.
Time frame: intraoperative
Genotype linkage analysis of the electrocardiographic response to ajmaline provocation in healthy subjects using candidate gene and gene wide association studies.
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Targeted genetic sequencing of the sodium channel genes SCN5A and SCN10A and gene wide association studies for rare variations
Time frame: through study completion, an average of 2 years