Ventricular Scar Mediated Arrhythmogenesis – V-SMART

The heart is an electrically activated mechanical pump. Its proper functioning
is facilitated by interaction between electrical and mechanical systems across
spatial scales and physics. Scar is associated with an increased propensity
for arrhythmia in the ventricles. Functionally, it alters activation patterns,
and mechanical force production, while exhibiting different tissue properties.
We hypothesize that electromechanical effects due to scar significantly
contribute to arrhythmogenesis. Modelling is the only methodology that can
currently examine electromechanical function at the resolution required. The
purpose of this project is to build models of infarcts, based on experimental
data, to elucidate arrhythmogenic mechanisms, and investigate potential
therapies.

Infarcts will be induced in a porcine model, with different densities of
surviving myocytes. In a Langendorff set up, mapping of activation,
repolarization, and ectopy will be performed, as well as arrhythmia
inducibility assessed, under different strains controlled by intraventricular
balloons. Scars will subsequently be imaged at very high resolution MRI and
microCT, as well as examined histologically.

Biological experiments will be replicated in silico to elucidate mechanisms
responsible, as well as inform how to best represent scar. The animal data
will be used to parameterize scars and tissue properties in detailed finite
element, electromechanical models built from the scanned porcine hearts.

Finally, clinical scans of patients experiencing post-infarct arrhythmias will
be used to create models. These models will be detailed with pericardial
boundary conditions, a closed circulatory system, a Purkinje networks.
Arrhythmogenicity will be confirmed in the model, scars categorized, and
various therapies explored.