Patient-Directed Computational Analysis of Atrial Fibrillation Project Summary Atrial fibrillation (AF) is the most common arrhythmia and is a rapidly-growing public health problem that currently affects over 30 million people world-wide and more than 5 million people in the US. If left untreated, AF leads to an increase in stroke, heart failure and mortality. Unfortunately, the mechanisms that maintain AF remain poorly understood, hindering further improvement of current therapy strategies. Recent studies, however, have revealed that AF may be driven by rotational or focal sources and that targeting these sources using localized ablation can result in promising long-term outcomes. Due to our incomplete understanding of AF, however, this targeted ablation approach is not always successful. This project will test the novel hypothesis that AF is sustained by localized rotational and focal sources with different size and temporal stability and that, after these sources are removed, termination is not immediate but is maintained by non-local mechanisms. We will address this hypothesis using a combined computational/clinical approach that employs advanced multiscale computational techniques and state-of-the-art clinical mapping. The project will 1) quantify AF organization using patient-specific geometries; 2) determine whether some rotational or focal sources are more important than others; 3) test possible causes of AF maintenance and termination using patient-specific digital computer models. We will use data from our unique and large patient registry, currently totaling >500 patients. This project is significant because it will establish a deeper understanding of AF and might reveal novel mechanisms of AF maintenance. Our results can be translated directly to practice and may enable the development of better treatment options.

Public Health Relevance

Atrial fibrillation (AF), the most common cardiac arrhythmia, affects more than 5 million people in the US and leads to increased morbidity and mortality. In this project, we will use a combined computational and clinical approach with the goal to increase our understanding of the mechanisms responsible for AF. This deeper understanding may result in more effective or new therapies for AF, a rapidly growing public health problem.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL122384-05A1
Application #
9973292
Study Section
Modeling and Analysis of Biological Systems Study Section (MABS)
Program Officer
Shi, Yang
Project Start
2015-01-12
Project End
2024-03-31
Budget Start
2020-04-01
Budget End
2021-03-31
Support Year
5
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of California, San Diego
Department
Physics
Type
Schools of Arts and Sciences
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Rogers, Albert J; Tamboli, Mallika; Narayan, Sanjiv M (2018) Integrating mapping methods for atrial fibrillation. Pacing Clin Electrophysiol 41:1286-1288
Zaman, Junaid A B; Sauer, William H; Alhusseini, Mahmood I et al. (2018) Identification and Characterization of Sites Where Persistent Atrial Fibrillation Is Terminated by Localized Ablation. Circ Arrhythm Electrophysiol 11:e005258
Vidmar, David; Alhusseini, Mahmood I; Narayan, Sanjiv M et al. (2018) Characterizing Electrogram Signal Fidelity and the Effects of Signal Contamination on Mapping Human Persistent Atrial Fibrillation. Front Physiol 9:1232
Vidmar, David; Rappel, Wouter-Jan (2018) To the Editor- On the deformation and interpolation of phase maps. Heart Rhythm 15:e3
Ho, Gordon; Villongco, Christopher T; Yousefian, Omid et al. (2017) Rotors exhibit greater surface ECG variation during ventricular fibrillation than focal sources due to wavebreak, secondary rotors, and meander. J Cardiovasc Electrophysiol 28:1158-1166
Zaman, Junaid A B; Baykaner, Tina; Clopton, Paul et al. (2017) Recurrent Post-Ablation Paroxysmal Atrial Fibrillation Shares Substrates With Persistent Atrial Fibrillation : An 11-Center Study. JACC Clin Electrophysiol 3:393-402
Zaman, Junaid A B; Kowalewski, Christopher A B; Narayan, Sanjiv M (2017) Mapping Ripples or Waves in Atrial Fibrillation? J Cardiovasc Electrophysiol 28:383-385
Alhusseini, Mahmood; Vidmar, David; Meckler, Gabriela L et al. (2017) Two Independent Mapping Techniques Identify Rotational Activity Patterns at Sites of Local Termination During Persistent Atrial Fibrillation. J Cardiovasc Electrophysiol 28:615-622
Lombardo, Daniel M; Rappel, Wouter-Jan (2017) Systematic reduction of a detailed atrial myocyte model. Chaos 27:093914
Zaman, Junaid A B; Rogers, Albert J; Narayan, Sanjiv M (2017) Rotational Drivers in Atrial Fibrillation: Are Multiple Techniques Circling Similar Mechanisms? Circ Arrhythm Electrophysiol 10:

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