The Maintenance of Human Atrial Fibrillation Project Summary. 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 outlines a program of career development for the applicant, of Mentored training for young clinician-scientists, and of mechanistic patient-oriented research in atrial fibrillation The Research Plan builds upon discoveries in the last cycle, that human AF is often not random, but instead 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 currently apply cautery therapy (ablation). In this project, we will study 1) how much additional benefit is achieved by ablating at trigger sites (at the pulmonary veins) over and above these rotor source; 2) how rotors actually cause disorganized rhythms, and not just simple organized circuits; 3) whether this process is altered by structural abnormalities in the atria. We will pursue these aims in a clinical trial, by making detailed recordings of AF, usin bioengineering methods and by integrating imaging. These patient-specific analyses will be among the most detailed and clinically-relevant in the field, and will form a platform for future hypothesis testing and clinical trials. This project is significant because it tests the success of novel therapy at recently discovered AF rotors against current standard-of-care, because it studies the fundamental mechanisms that cause cardiac fibrillation in humans, and because it also tests novel imaging strategies. This project will be performed in patients with AF and a limited number of patients without 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.
Atrial fibrillation (AF) is an enormous public health problem that affects 2-5 million Americans, causing stroke, rapid heart beats, 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 change our understanding of the disease and directly lead to new and more effective treatment.
| 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; 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 |
| 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 |
| 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 |
| Narayan, Sanjiv M; Vishwanathan, Mohan N; Kowalewski, Christopher A B et al. (2017) The continuous challenge of AF ablation: From foci to rotational activity. Rev Port Cardiol 36 Suppl 1:9-17 |
| Vidmar, David; Krummen, David E; Hayase, Justin et al. (2017) Spatiotemporal Progression of Early Human Ventricular Fibrillation. JACC Clin Electrophysiol 3:1437-1446 |
| Ni, Haibo; Whittaker, Dominic G; Wang, Wei et al. (2017) Synergistic Anti-arrhythmic Effects in Human Atria with Combined Use of Sodium Blockers and Acacetin. Front Physiol 8:946 |
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