Atrial fibrillation (AF) is the most common heart rhythm disorder, affecting 2-5 million Americans in whom it may cause skipped heart beats, dizziness, stroke and even death. Unfortunately, therapy for AF is limited. One of the major drawbacks in developing better therapy for AF is that our understanding of what causes AF (its 'mechanisms') is not clear. This renewal project builds on discoveries by this group in the last funding period that human AF is not random or chaotic, but instead is often maintained (driven) by a small number of 'sources'in the form of rotors (akin to electrical spinning tops) or focal beats, that are stable over time. Sources may lie in regions of the heart (the atria, or top chambers) that are different in each patient, often away from where physicians typically target cautery therapy (ablation). In this project, we will study 1) the effectiveness of ablation of rotos and focal sources alone (that drive AF);2) how ablation alters rotors, trigger sites near the pulmonary veins, or other mechanisms;3) the mechanisms for AF that may recur in some patients after ablation. We will pursue these aims by recording detailed maps of AF and studying several major possible mechanisms for AF in each subject. These studies will include detailed recordings of atrial tissue function, mathematical analyses of AF, detailed follow-up of patients after ablation and repeat study in patients in whom AF may recur. The patient-specific analyses that we will perform in this project will be among the most detailed and clinically-relevant in the field, and will be used to understand the disease and to help design better therapy. This project is significant because it will define the success of therapy at recently discovered novel mechanisms for AF and, in cases when such therapy is unsuccessful, we will study why. In this way, we will develop an approach to better define the causes (mechanisms) for AF in each patient. This project will be performed in patients with AF during electrophysiologic study, so that its results can be translated directly to practice. This approach may also allow a more rational general approach to drug development and gene therapy.

Public Health Relevance

Atrial fibrillation (AF) is an enormous public health problem that affects 2-5 million Americans, causing stroke, rapid heartbeats, heart failure and even death. In this project that builds on a successful previous funding period the applicant will perform research in patients to understand the precise causes (mechanisms) for AF that may alter paradigms in our understanding of the disease and lead immediately to new and more effective therapies.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL083359-06A1
Application #
8697547
Study Section
Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Lathrop, David A
Project Start
2005-12-01
Project End
2019-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
6
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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
Sahli Costabal, Francisco; Zaman, Junaid A B; Kuhl, Ellen et al. (2018) Interpreting Activation Mapping of Atrial Fibrillation: A Hybrid Computational/Physiological Study. Ann Biomed Eng 46:257-269
Baykaner, Tina; Rogers, Albert J; Zaman, Junaid A B et al. (2018) Editorial commentary: What can lung transplantation teach us about the mechanisms of atrial arrhythmias? Trends Cardiovasc Med 28:62-63
Navara, Rachita; Leef, George; Shenasa, Fatemah et al. (2018) Independent mapping methods reveal rotational activation near pulmonary veins where atrial fibrillation terminates before pulmonary vein isolation. J Cardiovasc Electrophysiol 29:687-695
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; 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
Baykaner, Tina; Zografos, Theodoros A; Zaman, Junaid A B et al. (2017) Spatial relationship of organized rotational and focal sources in human atrial fibrillation to autonomic ganglionated plexi. Int J Cardiol 240:234-239
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
Baykaner, Tina; Zaman, Junaid A B; Rogers, Albert J et al. (2017) Spatial relationship of sites for atrial fibrillation drivers and atrial tachycardia in patients with both arrhythmias. Int J Cardiol 248:188-195

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