Objectives of the Chair
This program focuses on improving the management of atrial fibrillation (AF) by advancing our understanding of the underlying mechanisms. AF is the most common sustained cardiac arrhythmia. Its management is challenging because of therapeutic failures and recurrences after apparently effective initial treatment. Age is the single most important factor determining the occurrence of AF, with the prevalence of the arrhythmia increasing exponentially after age 65, and the risk of AF increasing 7-fold by age 85. Furthermore, youth appear to be protected against AF, since individuals with congenital heart disease and severely diseased atria rarely develop AF before age 45. The basis for this age-dependence of AF is poorly understood. This program takes advantage of ongoing work at Liryc and complementary studies at the Montreal Heart Institute (MHI) that focus on the determinants of AF development.
Objectives of the project: To evaluate age-related factors which protect the hearts of younger individuals from AF and make older individuals more vulnerable.
The AF Chair project is performed in parallel with the ANR program Unmasc, with both projects addressing AF in experimental models.
Specific Objectives:
Expected Impact
The proposed work should provide important new insights into the mechanisms determining susceptibility to AF. The new knowledge obtained will improve our understanding of the arrhythmia and lead to the identification of new targets for therapeutic intervention. These targets will allow for improved treatments as well as strategies to improve the long-term success of existing approaches like catheter ablation.
Principal Collaborators @ Liryc
Objectives of the chair
The objective of the imaging chair is the development of highly advanced MRI methodology for detailed and quantitative characterization of myocardial tissue, anatomy, and function in the pursuit of new knowledge about the arrhythmogenic substrate and a better management of the disease. Another goal of this chair is sustainability of this research effort through education and promotion of young talent. To meet these objectives, the team leverage award-winning MRI methodology, state-of-the-art equipment, industrial collaborations, a track-record of world-leading expertise, an established international network, new mathematical concepts, and a history of successful interdisciplinary collaboration and translation.
Expected impact
This deliberate and dedicated endeavour will lead to new knowledge in the domain of cardiac arrhythmias, and to a non-invasive, more sensitive, and quantitative characterisation of the myocardial substrate. It will help us to better define success or failure of electrophysiology interventions, and it will provide us with a new and sensitive tool in the armamentarium of approaches to select patients who will be the most likely beneficiaries from Implantable cardioverter-defebrillator (ICD) placements. Finally, the next generation of world-leading experts will emerge from this initiative in support of longevity and sustainability.
Through a mechanistic, interdisciplinary, collaborative, and deliberate approach, we build on a substrate of established expertise and innovation, and will translate MRI methodology innovation from mathematical and physical concepts to phantom studies, in vivo studies, studies in healthy volunteers, and ultimately to patient studies in collaboration with medical professionals.
Collaborators @ Liryc
Ventricular Fibrillation Chair (Prof. Peng-Sheng Chen, Chair Holder)
Objectives of the chair
The main objective of the chair is to investigate the role of the nervous system in triggering and maintenance of arrhythmias and how ablation of the cardiac innervation can provide protection against these arrhythmias.
(1) We have developed a technique to simultaneously record the electrocardiogram (ECG) and the skin sympathetic nerve activity (SKNA). We call this technique the “neuECG”. We plan to record neuECG using commercially available devices. The first objective is to test the hypothesis that vein of Marshall (VOM) alcohol injection in humans can reduce the skin sympathetic nerve activity in patients with atrial fibrillation (AF). This will be tested in patients undergoing AF ablation. We plan to record neuECG before AF ablation, immediately after AF ablation and during follow up in patients without and with alcohol injection into the VOM.
(2) The second objective is to test the hypothesis that alcohol injection into the sympathetic nerve bundles near the left superior vena cava causes stellate ganglion remodeling. The ventrolateral cardiac nerve is a major source of sympathetic innervation to the free wall of the left ventricle. The nerve is located close to the VOM. We will inject alcohol into that nerve. We hypothesize that alcohol injection into the ventrolateral cardiac nerve will damage the axons and result in retrograde neuronal cell death in the stellate ganglion. That neural remodeling process will reduce the sympathetic output, resulting in the reduction of both SKNA and the plasma catecholamine.
Expected impact
Neuromodulation is a promising new method for managing patients with cardiac arrhythmias. Currently the clinical team at Liryc is a world-leader in using ethanol injection into the VOM for the management of atrial fibrillation. It is possible that the same technique can be used to manage ventricular tachycardia or fibrillation through neuromodulation. If the results show that ethanol injection into the VOM can successfully reduce the sympathetic outflow, then we will next perform experiments to determine if that technique can be used to control ventricular arrhythmias and prevent sudden cardiac death. Therefore, these research objectives may have significant impact on clinical practice.
Collaborators @ Liryc