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Principal Investigator: Ravi Ranjan
Organization: UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
Fiscal Year: 2024
Award: $763,469
Funding agency: National Heart Lung and Blood Institute
Ventricular tachycardia can be a life-threatening arrhythmia that requires effective and timely treatment. This
treatment often takes the form of catheter based ablation; however, the success rates are modest. Moreover,
the ablation procedure is invasive, done under general anesthesia, and can take many hours in patients who
already have compromised cardiac function, putting them at risk for more complications. Recently, radiation
therapy, like that used in oncology has been used to ablate cardiac arrhythmias. Initially performed in patients
who had run out of other options, the success in a few patients has opened the possibility of wider use.
However, despite this promising success, the biophysics of how radiation affects the cardiac tissue, the
timeline of scar formation, the acute and more chronic effect on the electrical propagation and the dose
response are all unknown. The time to response in radiation ablation in the reported studies is also highly
variable, ranging from immediate to more than 6 weeks for any results. More importantly, although radiation
ablation is non-invasive, it often requires an invasive electrophysiology study to identify the target site(s), an
essential step that determines the success or failure of the procedure. We propose to address both these
limitations by using our proven expertise in the fields of imaging, electrophysiology, computational modeling,
and radiation oncology to advance the use of radiation as a noninvasive means of ablation with the following
aims: (1) Determine the dose response and structural and functional effects of radiation on the cardiac tissue;
(2) Create radiation targeting strategies using personalized computational models of ventricular arrhythmias in
a pre-clinical VT model and patients; (3) Carry out non-invasive radiation ablation treatment in a pre-clinical
infarct model with ventricular tachycardia. In aim 1 we will address the biophysics of ablation by performing
electrophysiology studies at different time points after ablation with different doses to understand the effects of
radiation on electrical propagation. We will be doing serial MRIs to create a dose response and to evaluate the
heart for structural remodeling like edema, fibrosis, and scar. To provide a physiological basis for the effects,
we will do histology, protein expression analysis and confocal microscopy. In aim 2 we will use MRI to assess
patients with pre-existing ventricular scar and make personalized simulation models to determine the VT circuit
and the critical part of the circuit to target with radiation. Our existing database of VT patients, with MR images
and ECGs with VT and detailed map of the VT will provide the opportunity for validation of these models along
with a pre-clinical VT model. Finally, in aim 3 we will treat suitable VT pre-clinical model with radiation instead
of the traditional radiofrequency to further understand the mechanism underlying ablation with radiation.
Improving our understanding of the effects of radiation treatment for cardiac arrhythmias will fundamentally
change the way that patients with VT are managed, shortening procedure times, and reducing the risks
associated with invasive traditional ablation.
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